Exam 4 Flashcards

(258 cards)

1
Q

What does signal transduction allow cells to do?

A

Respond to chemical signals without allowing these chemicals into the cell

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2
Q

What is a signal transduction pathway?

A

a series of steps by which a signal received at the cell’s surface is converted into a specific cellular response

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3
Q

What are the three processes that cells receiving signals go through?

A

reception, transduction, response

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4
Q

What is direct cytoplasmic links and what are the different kinds? How does this effect plants in particular?

A

multicellular organisms can have cell junctions that directly connect the cytoplasm of adjacent cells:
Animals: gap junctions
Plants: plasmodesmata
Fungi: septum pores
this form of communication bypasses receptor-mediated transduction pathways. most signaling in animals doesn’t take place in this way. interconnected cytoplasm blurs the line between one cell and the next in a multicellular organism. This creates a vulnerability in plants as viruses are able to spread from one cell to another through plasmodesmata

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5
Q

Explain the origins of signal transduction and how this relates to quorum sensing

A

Microbes evolved the ability to detect and respond to stimuli like nutrients in the environment. This allowed signaling between bacterial cells to evolve and this is known as quorum sensing.

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6
Q

Discuss the process of quorum sensing

A

Free swimming microbes are vulnerable to environmental stresses. Some microbes land on a surface and attach. The cells start producing an extracellular matrix and secrete quorum sensing molecules. Quorum sensing triggers cells to change their biochemistry and shape. New cells arrive including new species and water channels form in the biofilm. Some microbes escape from the biofilm to resume a free-living existence and to form a new biofilm on another surface.

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7
Q

Discuss cell signaling range and how receptors relate to ligands

A

Cell signaling is accomplished through the release of a chemical messenger (signaling molecule) that diffuses some distance to its target receptor on another cell. The signaling molecule is the ligand of the target receptor. Receptors are highly selective for their ligands. Different types of signaling can be classified by the distance that the signaling molecule needs to diffuse to its target.

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8
Q

What is contact dependent signaling?

A

This is a form of signaling where a cell-surface bound ligand binds to a receptor on an adjacent cell. The ligand stays attached to the cell that made it and the cells travel to each other to communicate. This form of signaling is used to recognize other cells and identify their cell type. The cell surface-bound ligands are often glycolipids and glycoproteins.

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9
Q

Explain how cells know if they are attached to the extracellular matrix and how this relates to fibronectin.

A

Cells recognize if they are attached to the extracellular matrix through a form of contact dependent signaling. Integrins are receptors that anchor the cell to the ECM through an adaptor protein known as fibronectin. When fibronectin (ligand) is attached to the integrin (receptor) the cell will receive the normal signal from the integrin. If fibronectin is not bound to the integrin, it stops sending off signals to the rest of the cell.

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10
Q

What is paracrine signaling?

A

This is a form of local signaling where the signaling molecule is released from a cell into the extracellular fluid and nearby cells respond to the signal. The signaling molecules are called paracrine. Paracrine do not diffuse long distances and very little will enter the blood stream. Most cells can locally signal in this way, but specialized cells can use exocytosis to release their signaling molecules.

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11
Q

What is endocrine signaling?

A

This is a form of long-distance signaling where the signaling molecules are released from cells into the blood stream. The signaling molecules are transported throughout the body where they interact with target tissues. The signaling molecules are referred to as endocrines (hormones) and this form of signaling is referred to as hormonal signaling. These signaling molecules are released from a gland in the body, but other tissues can participate in this form of signaling.

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12
Q

What is neuronal signaling?

A

Neuronal signaling mixes the concept of local and long distance signaling. Neurotransmitters are released from the terminals of neurons directly onto their target cell (another neuron) and this is a localized form of signaling. The cell body of the neuron may be distant from its terminals, even meters away and this makes it a very long-distance form of signaling.

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13
Q

Where are neurotransmitters stored? When are they released?

A

Neurotransmitters are stored in the synaptic vesicles in the buttons of neuronal terminals. They are released only when an action potential reaches the terminal, and this causes an influx of Ca 2+ that stimulates exocytosis.

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14
Q

What is a synapse and how does this relate to diffusion time?

A

A synapse is a tight domain between two cells where neurotransmitters are released the diffusion time is very short. The exocytosis and diffusion of the neurotransmitter is much slower than the rate of the action potential propagation.

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15
Q

What is neuronal signaling also called? Neurons can partake in what type of signaling? and where can signaling also originate from

A

Neuronal signaling is also known as synaptic signaling but neurons can also participate in more paracrine like signaling where some neurotransmitter diffuses to more distant cells. Signaling can also originate from the post synaptic membrane and this is known as retrograde signaling.

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16
Q

What is the key to extracellular signals specific actions?

A
  1. the selective nature of their target receptors
  2. the signal transduction pathways these receptors couple to
  3. the combination of receptors on target cells
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17
Q

What can the same signaling molecule do and give an example

A

The same signaling molecule can induce different responses in different target cells; Different cell types respond to the neurotransmitter acetylcholine in different ways. Ach binds to similar receptors on heart pacemaker cells and salivary gland cells, but it evokes different responses in each cell type due to the receptors coupling to different signal transduction pathways. Skeletal muscle cells produce a different type of receptor for Ach

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18
Q

Explain cells and the dependency on extracellular signals and what the signaling molecules do

A

Cells depend on many extracellular signals. Every cell type displays a specific set of receptors that enable them to respond to a specific set of extracellular signal molecules produced by other cells. These signaling molecules work in combinations to regulate the behavior of the cell. The cell is blind to any signaling molecule that it cannot detect with a receptor.

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19
Q

Where do signaling molecules bind?

A

They bind at a specific site on the receptor called the orthostatic site

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20
Q

What are endogenous ligands? What does equilibrium favor?

A

Endogenous ligands are agonists, and they promote the activity of the receptor. Receptors are constantly changing conformation; equilibrium favors an inactive states of the receptor

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21
Q

What are agonists?

A

Agonists stabilize an active conformation of the receptor through induced fit

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22
Q

What are antagonists?

A

compounds that compete for binding with agonists (blocking them from binding) and may also stabilize an inactive form of the receptor

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23
Q

Where do extracellular signaling molecules bind?

A

They bind to either cell-surface receptors or intracellular receptors

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24
Q

What happens to large and hydrophilic extracellular signal molecules?

A

They are unable to cross the plasma membrane directly and bind to cell-surface receptors instead

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25
What happens to small hydrophobic extracellular signal molecules? and give an example of these hydrophobic messengers.
they pass through the target cell's plasma membrane through passive, simple diffusion. They bind and activate the intracellular receptors (in cytosol or nucleus) that then regulate gene transcription or other functions. An example of these messengers are steroid hormones. An activated steroid hormone receptor complex can act as a transcription factor and turn on specific genes.
26
Where are receptors located?
most receptors span the plasma membrane and the orthosteric site faces outward.
27
Explain Ligand-Gated Ion Channels and give an example
LGIC is a receptor that acts as a gateway for the flow of specific ions through the plasma membrane in response to a stimulus. This is facilitative transport and will only flow down the gradient. Ligands do not cross the membrane only ions do. These channels directly impact the membrane potential of cells specifically neurons and muscle tissue. LGIC interaction with neurotransmitters glutamate and GABA account for 95% of the synaptic activity in the brain. Enzymes and other intracellular receptors are sensitive to specific ions and this results in multiple transduction pathways being activated.
28
Explain receptor tyrosine kinases
Kinases are enzymes that phosphorylate other proteins. RTKs are plasma membrane receptors that auto-phosphorylate their own tyrosine residues in response to a stimulus. RTK can trigger multiple signal transduction pathways at once. Abnormal functioning of RTKs is associated with many types of cancer.
29
What are G-protein coupled receptors? What are they made of? and what are their importance?
GPCR are composed of 7 transmembrane domains, 3 intracellular loops, 3 extracellular loops and a large intracellular c-terminus. GPCR is a plasma membrane receptor that works through a transduction molecule called a G protein. 4% of human genes code for GPCRs and many have alternative splicing variants. GPCR activity initiates and regulates many intracellular signaling pathways that overlap with pathways initiated by RTKs
30
Go through the five families that are part of the GPCR family and their parts in the GRAFS system
Glutamate - ions and small molecules Rhodopsin - ligands ranging from light, small molecules, peptides to proteins Adhesion - ligands mostly unknown Frizzled - Wnt proteins Secretin - peptide hormones
31
What are G-proteins?
G-proteins are guanine nucleotide-binding proteins. They occur as monomeric small GTPases and heterotrimeric G-proteins that associate with GPCRs
32
What is inside Heterotrimeric G-proteins
Alpha subunit - binds GTP (active state) and hydrolyzes it to GDP (inactive). this subunit is the signal transduction protein of greatest interest and variation Beta and gamma subunits- forms a stable dimer called the B/y complex. able to initiate signaling pathways when the alpha subunit binds GTP and disassociates from the heterotrimer.
33
Explain GTP Exchange and the on/off switch for a G-protein
Agonists stabilize active confromations of GPRCs, allowing the receptor to act as a guanine nucleotide exchange factor. GPCRs turn on G-proteins by interacting with them and swapping out GDP for GTP. GTP/GDP acts as the on/off switch for a G-protein. When bound to GTP the G-protein is active and can activate enzymes that produce second messengers. When bound to GDP the G-protein is inactive. GPCRs also signal through G-protein independent pathways.
34
Talk about G protein a subunit and the different types
a subunit forms several families based on the second messenger systems they influence: Gas - stimulates cAMP production Gai and Gao - inhibit cAMP production Gaq - stimulates phospholipase C
35
Talk about B/y subunits and signaling
B/y subunits also activate signaling pathways and a primary one is the activation of GIRK channels
36
Talk about the first messenger and what occurs
The extracellular signaling molecule that binds to the receptor is the pathway's first messenger. The signaling molecule is received by the receptor which transduces the signal via conformational change of the receptor. This is followed by the rest of the signal transduction pathway which involves multiple steps
37
Talk about second messengers
Second messengers are small, non-protein, water soluble molecules or ions that are synthesized or released as part of a signal transduction pathway. Second messengers participate in pathways initiated by GCPRs and RTKs. cAMP and Ca 2+ are common second messengers.
38
What is cAMP?
one of the most widely used second messengers in cells
39
What is adenylate cyclase?
an enzyme in the plasma membrane that converts ATP to cAMP in response to Gs proteins and other stimuli
40
What does phosphodiesterase do?
ends cAMP second messenger signaling by converting cAMP to AMP
41
How is the formation of cAMP triggered?
Signal molecules trigger the formation through GPCRs
42
How does protein kinase A phosphorylate other proteins?
cAMP activates protein kinase A (PKA)
43
How is adenylate cyclase inhibited?
Activation of Gi/o proteins inhibits adenylate cyclase which counters the effects of Gs proteins lowering the cellular cAMP levels
44
How is cytosolic concentration of Ca 2+ regulated?
Cells regulate the cytosolic concentration of Ca 2+ by pumping Ca 2+ into the ER, out of the cell, or into other compartments
45
What are the pathways that lead to the releasement of Ca 2+ and the process that goes a long with this.
Pathways that lead to the releasement of Ca2+ involve inositol triphosphate (IP3) and diacylglycerol (DAG) as upstream messengers: GPCRs can activate Gq proteins which can then activate phospholipase C. PLC catalyzes the production of IP3 and DAG by hydrolyzing phosphatidylinositol (PIP2). IP3 acts as a second messenger and bind IP3 LGICs on the ER, releasing Ca2+ into the cytosol. Ca2+ and DAG go onto activate other proteins.
46
Explain agonists role in terminating GPCR and when G-protein signaling will end.
Agonists interact with the GPCR binding site in a reversible manner and agonist bound receptors cease signaling when agonist dissociates. Prolonged exposure to agonist will result in the desensitization of the receptor. G-protein signaling will end when G-protein-couples receptor kinases (GRKs) phosphorylate intracellular domains of the GPCR, interfering with G-protein association.
47
Talk about arrestin, what happens to receptors if they are desentized and down regulation
Receptor phosphorylation recruits arrestin proteins (B arrestin). Desenstitized receptors may be internalized and recycled back to the plasma membrane or degraded. Internalized receptors may still signal through arrestins until they are recycled. Down-regulation refers to a decrease in expression level of receptors on the cell surface
48
How is a signal transmitted in many pathways?
A signal is transmitted by a cascade of protein phosphorylation. GPCRs and LGICs rely on second messengers (ions in the case of LGICs) to induce phosphorylation cascades. RTKs skip directly to the phosphorylation step
49
What is dephosphorylation? What does it act like? What does phosphorylation alter?
A process where protein phosphatases remove the phosphates from proteins, a process called dephosphorylation. Phosphorylation and dephosphorylation act as a molecular switch turning activities on/off. Phosphorylation alters the shape of the proteins and affects the protein's activity.
50
What the final protein the signaling cascade called?
effector protein
51
Explain enzymes cascades and amplification
Enzyme cascades amplify the cell's response. At each step the number of activated products is much greater than in the preceding step. A single ligand binding receptor produces a response that can amplified many thousands or millions of times by signal transduction.
52
Explain signal specificity and give an example
cells can have different receptors for the same signaling molecule. these different receptors might respond to the signaling molecule in different ways they can couple to different transduction pathways. Dopamine released in the striatum can excite or inhibit neuronal activity depending on the presence of different receptors in the cells. D1 receptors couple to Gs and excite neurons. D2 receptors couple to Gi/o and inhibit striatal neurons.
53
What is pathway branching?
occurs when different signal transduction pathways are available for a receptor
54
What is pathway cross-talk
helps the cell coordinate incoming signals
55
What is the role of scaffolding proteins?
scaffolding proteins are large relay proteins to which other proteins are attached. They increase the signal transduction efficiency by grouping together different proteins involved in the same pathway. Scaffolding proteins may help activate some of the relay proteins.
56
What is the most direct means of signal termination or prolongation?
The most direct means is through modulating the signaling molecule's extracellular concentration. If the concentration falls fewer receptors will be bound. Unbound receptors are in an inactive state.
57
What happens in termination or prolongation of the signal in relation to transporters and give an example
Transporters clear neurotransmitters from synapses. For example serotonin-reuptake transporter (SERT) clears serotonin by transporting it back into the presynaptic neuron
58
What happens to extracellular enzymes in relation to termination
Extracellular enzymes degrade neurotransmitters for example acetylcholinesterase degrades ACH in neuromuscular junctions
59
What is the cell's ultimate response to a signal?
this is called the output response; effector proteins directly mediate this response
60
What are outcomes of an output response?
A change in cytoplasmic activities A change in gene transcription; this will ultimately lead to a change in cytoplasmic activities
61
What is the cytoskeleton composed of
a dynamic network of proteins arranged in long intertwined filaments in the cell
62
What does the cytoskeleton do?
provides support for cellular contents and maintains the shape of the cell
63
What can much of the cytoskeleton do?
grow, shrink, or be restructured dynamically
64
What do motor proteins that associate with the cytoskeleton do?
harness energy stored in ATP to propel themselves along the cytoskeleton or exert force on the cytoskeleton
65
What comes together to give us muscle contraction?
motor proteins and the cytoskeleton
66
What are the three types of filaments in the cytoskleton?
microtubules, actin filaments, intermediate filaments
67
Of the three types of cytoskeletons which has the largest diameter?
microtubles
68
what are microtubules composed of?
protein subunits called ab tublin dimers. tublin dimers polymerize into a cylinderical structure; the inside of the cylinder is hollow
69
what are the mechanical properties of microtubules?
Microtubules are strong, more rigid than other cytoskeleton, able to resist compression but don't do well with tension
70
Rapid polymerization and depolymerization of the ab tubulin subunits does what?
allows the microtubules to grow and shrink which makes them a very dynamic part of the cytoskeleton
71
What type of cells almost always has microtubules and where are they growing out of?
animal cells; centrosome
72
During what process and what forms mitotic spindles?
mitosis; bundles of microtubules
73
What organisms have microtubules at their core and what motor protein is involved with these organisms
cilia and eukaryotic flagella; the motor protein dynein exerts force on the microtubules and causes cilia and flagella to bend and whip
74
What do microtubules do for the cell's shape?
they provide reinforcement for the cell's shape and resist compression of the cell
75
Talk about the dimers involved in microtubules and their orientation
the dimers polymerize into a protofilament, one ab tublin dimer stacked lengthwise on top of the next; B-tublins are always at the growing end of the microtuble. As the protofilaments grow in length, they anneal to neighboring protofilaments. Each microtuble is composed of 13 protofilament in staggered parallel alignment
76
Where do the ab tublin dimers begin polymerization?
nucleation sites on the centrosome and these sites have a y-tubulin ring complex
77
Talk about the minus and plus end of the microtubles
the minus end of each microtubule is embedded in the centrosome and the plus end of each microtubule extends into the cytoplasm. The free plus ends are dynamically unstable and switch from uniform growth to rapid shrinkage.
78
Where can new microtubules be grown?
centrosome
79
When microtubules bundle together what do they form?
they form mitotic spindles to aid in the segregation of chromosomes during mitosis
80
What anchors microtubles?
basal bodies anchor microtubules that makeup the cores of cilia and flagella
81
Talk about Microtubles dynamic
microtubules display dynamic instability, each microtubules grows and shrinks independently of its neighbor
82
how are microtubules stabilized?
by attaching to capping proteins, these prevent depolymerization
83
What happens to microtubules without capping proteins?
they continue to grow or become unstable and depolymerize, losing their subunits from their plus ends
84
What drives dynamic instability on microtubules?
Dynamic instability is driven by GTP hydrolysis - ab tublin dimers must be bound to GTP to polymerize. the GTP binding site is on the B-tublin polypeptide
85
What happens once GTP is hydrolyzed to GDP in relation to microtubules
ab tublin dimers will not bind as tightly as other dimers, the protofilaments cannot grow
86
What happens if GTP hydrolysis outpaces polymerization?
the protofilaments peel away and the ab subunits detach
87
How do motor proteins move along microtubles?
using their globular heads, they hydrolyze ATP to power their stepwise movement
88
What way does the motor protein dynein move?
towards the minus end
89
what way does the motor protein kinesin move?
towards the plus end
90
How can motor proteins attach to cargo and what can cargo be?
They attach through adapter proteins. cargo can be large proteins, vesicles, and other cellular components
91
The microtubules network of the cell and the different motor proteins can do what?
the microtubule network of the cell and the different motor proteins with their adaptors can carefully position cellular components within the cell. The components are usually anchored in place by intermediate filaments.
92
cilia and flagella have what type of microtubules and how are their movements caused?
stable microtubules, their movements are caused by force exerted by dynein
93
Talk about linker proteins in relation to microtubules and dynein
Linker proteins do not allow microtubules to slide away from each other. Dynein is bound to one set of microtubules and attempts to move exert force against an adjacent set of microtubules. Because the microtubules cannot slide against each other they bend, producing a power stroke. When available ATP has been hydrolyzed, the microtubules relax.
94
Which has the smallest diameter of the cytoskeleton
Actin filaments
95
What is Actin filaments composed of?
subunits called actin, actin assembles into quaternary structure of two parallel chains of actin subunits wrapped together into a helix
96
What is the mechanical properties of actin filaments
rope like structure, they can resist tension however a single helix cannot resist compression through a network of intertwined actin filaments some compression can be bared
97
Talk about rapid depolymerization and polymerization of actin subunits
allows actin filaments to grow and shrink which makes them very dynamic part of the cytoskeleton
98
How are actin filaments organized
linear bundles to provide greater strength
99
What types of networks form within the cells in relation to actin filaments
two and three dimensional networks form gels within cells; growth of these networks allows the extension of cytoplasm for cell growth, migration and formation of psudopods
100
talk about the assembly of actin filaments
actin monomers carry ATP which is hydrolyzed to ADP after assembly into a growing filament. The ADP molecules remain bound within the actin filament. When ATP actin adds to the plus end of an actin filament at the same rate that ADP actin is lost from the minus end, treadmilling occurs the filament migrates.
101
What happens after actin filaments assemble
actin-binding proteins control the behavior of actin filaments in cells. This makes actin filaments highly adaptable to changes in the cell and gives actin filaments many roles.
102
What is the region of the cell richest in actin filaments?
The cortex. this region underlies the plasma membrane of most eukaryotic cells.
103
What helps move a cell forward?
forces made in the actin filament rich cortex. this is accomplished through the treadmilling process of actin filaments
104
What can alter the arrangement of actin filaments? And how does this relate to the Rho-family GTPases
Extracellular signals can alter the arrangement of actin filaments. The Rho-family GTPases can have a dramatic effect on the organization of actin filaments in fibroblasts
105
How are contractile structures formed?
actin associates with myosin
106
what is myosin
a motor protein that moves along actin filaments towards the plus end
107
How is myosin I used in cells
similar to how motor proteins are used with microtubules
108
How is myosin II used in the cell
myosin II can form filaments of its own and this is the base for the construction of muscle tissue
109
Talk about the contraction of interacting actin and myosin-II filaments in both muscle and non-muscle cells
Small bipolar myosin-II filaments can slide two actin filaments of opposite orientation past each other. A myosin II head group walks towards the plus end of the actin filament. Multiple myosin molecules are needed to generate this movement. When one myosin head releases the filament to reposition itself the other myosin must stay attached so the structure doesn't fall apart.
110
What are sarcomeres? and how are they arranged?
contractile units of muscle; stacked together into myofibrils within muscle cells
111
What are Z-discs and where are they located?
Z discs at either end of the sarcomere are attachment points for the plus ends of actin filaments
112
Where are thick filaments located and what are they made of?
they are centrally located thick filaments and are each composed of many myosin-II molecules
113
Talk about myosin in relation to the lever arm, ATP, and ADP
Myosin is attached to actin before ATP binds. ATP binding reduces myosin's affinity for actin. This reduces the affinity of the head for actin and allows it to let go of the filament. ATP hydrolysis, and the release of inorganic phosphate, triggers the power stroke that returns myosin to its original rigor configuration. At the end of the cycle the myosin head moved to a new position on the actin filament and is ready for the next cycle.
114
Talk about muscle contraction and transverse tubules
transverse tubules and the sarcoplasmic reticulum surround each myofibril. muscle contraction is triggered by a sudden rise in cytosolic Ca 2+
115
How is skeletal muscle contraction triggered?
release of Ca 2+ from the sarcoplasmic reticulum into the cytosol. this is controlled by tropomyosin and troponin complexes
116
Talk about the regions of tropomyosin
the tropomyosin molecule has seven evenly spaced regions each which binds to an actin monomer in the filament
117
What leads to the movement of tropomyosin away from the myosin-binding sites
Troponin anchors tropomyosin and Ca2+ binding to the troponin complex
118
what happens once the myosin binding sites are revealed?
ADP bound myosin can attach and contractile force can be excreted.
119
What are intermediate filaments made of
fibrous polypeptides arranged in parallel coils, keratin, they cannot be rapidly assembled or dissembled
120
Talk about the mechanical properties of intermediate filaments
they are strong and able to resist compression and tension
121
Out of the three cytoskeleton which is the least dynamic?
intermediate filaments
122
What do intermediate filaments act as
They are more permanent structures inside cells and act as anchor points for organelles
123
What is the nuclear lamina and what is it made out of
the inner side of the nuclear envelope is lined with intermediate filaments made of lamin to provide strength and shape to the nucleus
124
Intermediate filaments often connect what and what occurs
cell-cell junctions on one side of the cell to the other side, spanning the cytoplasm; this allows force applied to the cell to be distributed throughout the cell and the tissue they are embedded. this is common in epithelial tissue
125
Where are most intermediate filaments found
around the nucleus and extend out to the cell-cell junctions called desmosomes
126
What strengthens cells against mechanical stress
the durability and moderate rigidity of intermediate filaments
127
Why will different cell types need different intermediate filaments? give an example
to cope with their roles in the body and the stresses they are under. 50 different genes for keratin and keratin like proteins exist in humans and their products can be assembled into different classes of intermediate filament
128
What can happen if there are defects in intermediate filament networks
skin cells (karatinocytes) can lift off from the basal lamina due to malformed filament networks, this results in excessive blistering in response to only mild pressure applied to the skin
129
How is the nuclear lamina composed? What does the nuclear lamina do? What does mutations in lamin genes cause?
Lamin proteins form a lattice of intermediate filaments called the nuclear lamina that lines the inner face of the nuclear envelope. This supports and strengthens the nuclear envelope and provides attachment sites for the chromosomes. Mutations in lamin genes can result in malformed nuclear lamina and are related to accelerated cell death and aging in progeria
130
What do links between intermediate filaments of the nuclear lamina and other cytoskeletal protein networks do?
These links penetrate the nuclear envelope, anchoring the nucleus in place and bridging the nuclear lamina to other proteins including plectin
131
What is plectin?
Plectin is a linker protein that aids in the bundling of intermediate filaments and links these filaments to other cytoskeletal protein networks
132
What is the cell cycle
growth and division of eukaryotic cells
133
What is mitosis
cell division that results in daughter cells with identical genetic information
134
What is meiosis
special type of division that can produce sperm and egg cells; these daughter cells have different genetic information compared to their parent cells
135
What is the Mitotic phase (M phase)
division of nuclear contents through mitosis and the division of the cytoplasmic contents through cytokinesis
136
What is interphase?
takes up 90% of the cell cycle and can be divided into sub-phases G1, S-phase, G2
137
What occurs in G1 phase
cell growth
138
What occurs in S phase
cell growth and DNA replication
139
What occurs in G2 phase?
cell growth and preparation for M phase
140
What is the purpose of the cell cycle control system?
ensures that processes in the cell occur in the proper sequence and at the proper time
141
What can the control system do at specific times?
halt the cycle at specific transition points during G1, G2, and M phase. the cycle can halt if extracellular or intracellular conditions are unfavorable
142
What does progression through the cell depend on?
Cyclin-dependent protein kinases Cdks
143
How does Cdk become activated?
binds to a regulatory protein cyclin
144
How does the accumulation of cyclins regulate the activity of Cdks?
the formation of active cyclin-Cdk complexes drives cell cycle events including entry into S phase or M phase. types of cyclin that accumulate and types of Cdks that they activate differ as the cell moves through the cell cycle.
145
What do different cyclin-CDK complexes do? Why is it important to regulate the concentrations of cyclins?
Different cyclin-CDK complexes trigger different steps in the cell cycle. regulating the concentrations of cyclins is critical to proper cell cycle control
146
How is the activity of some Cdks regulated?
cyclin degradation
147
What must happen for M-CDK to be active? Explain this process
Inhibitory phosphates have to be removed. As soon as the M cyclin-Cdk complex is formed it is phosphorylated at two adjacent sites by the inhibitory protein kinase called Wee1. This keeps M-CDK in an inactive state until the phosphates are removed by an activating protein phosphatase called Cdc25.
148
For many cells what check point is the most important? If a cell receives the go ahead at G1 what must happen?
G1; it must complete the S, G2, and M phases and divide or it will not survive.
149
What happens if a cell doesn't receive the go ahead signal at the G1 checkpoint?
it will exit the cycle and go into G0 phase. some cells in G0 may exit this phase and re-enter the cell cycle. cells can also terminally differentiate. this is referred to as G0 however they cannot re-enter the cell cycle.
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Where do cells do most of their growing?
G1 phase
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What do mitogens do?
promote the production of the cyclins that stimulate cell division. mitogens stimulate cell proliferation by inhibiting the Rb protein.
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What happens if there is DNA damage in G1?
it can stop the cell cycle in G1. When DNA is damaged, specific protein kinases respond by activating p53 protein and halt its degradation. p53 protein accumulates and stimulates the transcription of the gene that encodes the Cdk inhibitor protein p21. the p21 protein binds to G1/S-Cdk and S-CDK inactivates them so the cell cycle stops in G1.
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In S Phase what does S-CDK do?
initiates DNA replication and blocks multiple rounds of DNA replication.
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What occurs in the initiation of DNA replication steps?
During G1, Cdc6 binds to the origin recognition complex (ORC) and these proteins load a pair of DNA helicases on the DNA to form prereplicative complex. At the beginning of S-phase S-Cdk triggers the firing of the loaded replication origin by guiding the assembly of the DNA polymerase and other proteins that initiate DNA synthesis at the replication fork.
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What can happen if there is incomplete replication?
the cell cycle can be arrested in the G2 phase
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What is replicated besides DNA in G2? and what are the critical processes in G2?
Centrosomes; Checking for completion of DNA replication and detecting DNA damage
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How does M phase start and end?
starts with mitosis and ends with cytokinesis
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Mitosis is usually divided into five stages: What happens in Prophase
replicated chromosomes condense into sister chromatids. the mitotic spindles start to assemble
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Mitosis is usually divided into five stages: What happens in Prometaphase
nuclear envelope dissipates, Chromosomes attach to mitotic spindles. Chromosomes assist in the assembly of mitotic spindles
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Mitosis is usually divided into five stages: What happens in Metaphase
sister chromatids align along the metaphase plate
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Mitosis is usually divided into five stages: What happens in Anaphase
proteolysis triggers sister chromatid separation during anaphase. an unattached chromosome will prevent sister-chromatid separation
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Mitosis is usually divided into five stages: What happens in Telophase
nuclear envelope reforms and chromosomes dissipate into less condensed chromatin structures
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What drives entry into mitosis?
M-Cdk drives entry into mitosis
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What does Activated M-Cdk do?
indirectly activates more M-Cdk and this creates a positive feedback loop. Once activated M-Cdk phosphorylates and activates more Cdk-activating phosphatase (Cdc25). This phosphatase can now activate more M-Cdk by removing the inhibitory phosphate groups from the Cdk subunit. This loop builds on itself until all M-Cdk is activated.
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What does cohesin do?
tie together the two adjacent sister chromatids in each duplicated chromosome
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What does condensin do?
help coil each chromatid into a smaller, more compact structure that can be more easily segregated during mitosis
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Where do mitotic spindles grow out from?
centrosomes
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Where do centrosomes go during early M phase?
opposite poles of the cell
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What is an aster and when does this begin?
the outgrowth of mitotic spindles. begins in prophase
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How is a bipolar mitotic spindle formed
by the selective stabilization of interacting microtubles
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What is an overlap zone
when two microtubles from opposite centrosomes interact. motor proteins and other microtuble-associated proteins cross link the microtubules together to stabilize the plus ends
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What are kinetochores? Give some information about them
protein structures located as the centromeres of chromosomes. This is also the attachment point where sister chromatids attach to opposing mitotic spindles.
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Each mitotic spindle is composed of what and where do kinetochores bind?
composed of multiple microtubules. The kinetochore binds to the plus ends.
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How are microtubules attached to mitotic spindles
via interactions with multiple copies a connecting protein complex
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What are astral microtubules
stabilize the position of centrosomes at the poles of the cell
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What are kinetochore microtubules
attach to chromosomes
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What are interpolar microtubules?
stabilize the position of the centrosome relative to each other provide counter force for chromatid separation
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What is the metaphase plate?
an imaginary 2D structure at the midway point between the spindle's two poles
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What triggers sister chromatid separation at anaphase?
proteolysis of cohesins
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During separation of chromatids what happens to the sister chromatids?
They separate and move along the kinetochore microtubules toward opposite ends of the cell
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How do microtubules shorten?
depolymerize at their kinetochore ends
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How do chromosomes move on microtubules?
Kinetochore microtubules do not pull on the chromosomes, the chromosomes move down these microtubules, depolymerizing the αβ tubulin dimers as they go
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What is Anaphase A?
separation of sister chromatids, chromatids move towards centrosomes
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Anaphase B
centrosomes move apart from each other, the cell elongates
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How is the nuclear envelope disassembled and reformed during mitosis?
The phosphorylation of nuclear pore proteins and lamins helps trigger the disassembly of the nuclear envelope at prometaphase. Dephosphorylation of these proteins at telophase helps reverse the process
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How is the cleavage furrow formed?
action of the contractile ring of actin and myosin filaments at the plasma membrane
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The interpolar microtubules recruit proteins that do what during cytokinesis?
generate a signal that activates a protein called RhoA in the cell cortex
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What does RhoA do?
a member of the Rho family of GTPases, controls the assembly and contraction of the contractile ring of actin filaments midway between the spindle poles
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What happens to the contractile ring in cytokinesis? What happens to the organelles?
The contractile ring divides the cell in two Organelles must be distributed to daughter cells when a cell divides
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What is necrosis and how is it caused?
can be caused by many events (e.g., rupture of the plasma membrane, high heat, poisoning of critical metabolic pathways, viral infection) and results in a messy cell death
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What is apoptosis?
is tightly controlled and initiated under particular circumstances, driven by a cascade of cellular responses that cleanly breaks down the cellular structure so the cell remnant can be eliminated by phagocytic cells
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What is apoptosis's role in development?
helps to sculpt or reshape tissues during development.
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What is apoptosis's role in neuronal development?
The earlier stages of nervous system development results in an overproduction of neurons in the brain. Some cells will receive insufficient amounts of survival factor to keep apoptosis suppressed. This strategy of overproduction followed by culling can help ensure that all target cells are contacted by neurons and that the extra neurons are automatically eliminated
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What is a benign tumor
abnormal cells remain at original site
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What are malignant tumors
invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors
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How is apoptosis mediated
intracellular proteolytic cascade
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Initiator caspase is first made as what?
an inactive monomer called procaspase
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Apoptotic signals trigger what?
the assembly of adaptor proteins that bring together a pair of initiator caspases and activate this leads to cleavage of a specific site in their protease domains
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Executioner caspases are initially formed as what? Upon cleavage by an initiator caspase what happens?
initially formed as inactive dimer procaspases; the executioner caspase dimer undergoes an activating conformational change
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What happens when the executioner caspases cleave a variety of key proteins?
apoptosis
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What happens when Bak or Bax proteins are activated by an apoptotic stimulus?
they aggregate in the outer mitochondrial membrane leading to the release of cytochrome c into the cytosol. Cytochrome c then binds to an adaptor protein and causes it to assemble into a complex called the apoptosome. This complex recruits seven molecules of procaspase-9.
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What happens when the procaspase-9 proteins become activated within the apoptosome?
they activate executioner procaspases in the cytosol
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How do survival factors supress apoptosis?
regulating Bcl2 family members
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Extracellular growth factors increase and decrease what?
increase the synthesis of macromolecules and decrease degradation of macromolecules
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Binding of a growth factor to RTK does what
initiates an intracellular signaling pathway that leads to activation of a protein kinase called Tor which acts through multiple targets to stimulate protein synthesis and inhibit protein degradation
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Frequency of cell division varies with cell type and is tightly regulated by internal and external signals give an example of an internal and external signal
internal signal: kinetochores that are not attached to the spindle microtubules send a molecular signal that delays anaphase. external signals are growth factors, proteins released by certain cells that stimulate other cells to divide
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What is density-dependent inhibition
Example of external signals controlling cell growth where the crowded cells stop dividing
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What is anchorage dependence
animals cells must be attached to a substratum in order to divide
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Cancer cells that are not eliminated by the immune system form what?
tumors
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What is asexual reproduction?
single individual passes genes to offspring without fusion of gametes. a clone is a group of genetically identical individuals from the same parent
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What is sexual reproduction
two parents give rise to offspring that have unique combinations of genes inherited from the two parents
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How many sets of chromosomes do animal somatic cells have and gametes have?
2 sets; 1 set
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What are homologous chromosomes?
when cells have more than one set of chromosomes that code for the same gene
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What are alleles
different variations of a gene
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What is a karyotype
ordered display of the pairs of chromosomes from a cell halted at or just before metaphase
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How many chromosomes are in each somatic cell
2 sets of 23 one set from each parent
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What is cytogenetic analysis?
analysis of bands on chromosomes which can be used to diagnose diseases based on abnormal number of chromosomes or abnormal chromosomal structure
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Talk about genes on the Y chromosome
few genes and they are related to sex characteristics
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How can individuals develop sexual characteristics that differ from their genetic makeup
abnormal hormonal regulation of the mother or fetus which results in incorrect release of sex hormones during development in utero
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What is a zygote and how many sets of chromosomes does it have?
a fertilized egg and it 1 set of chromosomes from each parent
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Plants and some algae exhibit an alternation of generations what does this mean?
both the diploid and haploid generations have a multicellular stage
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the gametes of plants and algae undergo what and what does this lead to?
mitosis which leads to multicellular haploid organism called a gametophyte which makes additional gametes for fertilization by mitosis
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What happens when gametes merge? in relation to plants
a zygote is formed and grows by mitosis; the diploid organism that develops is called the sporophyte
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How do sporophytes make spores? How do the spores grow?
meiosis; they grow by mitosis into haploid gametophyte
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For fungi and protists what is the diploid stage?
the only diploid stage is the single-celled zygote and there is no multicellular diploid stage
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In fungi and protists how does the zygote produce haploid cells?
meiosis
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Meiosis takes place in how many cell divisions?
two sets of cell divisions called meiosis I and meiosis II but only one round of DNA replication
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What happens in Meiosis I
reductive division - homologous chromosomes pair up and separate resulting in two haploid daughter cells with replicated chromatids but with only half the genome of the parental cell
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What happens in meiosis II
equal division - sister chromatids separate like in mitosis meiosis follows a similar pattern to mitosis however the result is four haploid daughter cells with unreplicated chromosomes
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What is oogenesis?
process of producing an egg cell; only one gamete is formed
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what is spermatogenesis
produce sperm cells; four daughter cells are formed by meiosis each are functional gametes
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What occurs in Prophase I
chromosomes begin to condense, at synapsis homologous chromosomes loosely pair up aligned gene by gene resulting in crossing over where non-sister chromatids exchange DNA segments. each pair of chromosomes forms a tetrad, a group of four chromatids. each tetrad has one or more chiasmata (x shaped region where crossing over happens)
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What does crossing over do?
produces recombinant chromosomes, which combine DNA inherited from each parent into a single chromosome, contributing to genetic variation of a population
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How does the process of homologous recombination begin?
protein complexes produce a double stranded break in the DNA of one of the chromatids
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Proteins that are involved in homologous recombination then do what
promote the formation of a cross strand exchange with the undamaged chromatid. once this occurs each chromatid has a segment of DNA from the other
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steps that produce chromosome cross overs during meiosis resemble what
that guide the repair of DNA double-stranded breaks in somatic cells
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What does the synaptonemal complex do
helps align the duplicated homolog pairs
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What are axial cores
protein structures that run the length of each chromosome they bind to the cohesion holding the sister chromatids together
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How do axial cores interact with each other
through adaptor proteins called transverse filaments
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crossover events create what?
chiasmata between non-sister chromatids in each bivalent forming a tetrad
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What happens in metaphase I in meiosis
tetrads line up at the metaphase plate, with one chromosome facing each pole Microtubules from one pole are attached to the kinetochore of one chromosome of each tetrad Microtubules from the other pole are attached to the kinetochore of the other chromosome
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What happens in Anaphase I in meosis
pairs of homologous chromosomes separate One chromosome moves toward each pole, guided by the spindle apparatus Sister chromatids remain attached at the centromere and move as one unit toward the pole
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What happens in telephase I in meosis
each half of the cell has a haploid set of chromosomes; each chromosome still consists of two sister chromatids
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What happens in cytokinesis in meiosis
two haploid daughter cells are formed. in the production of sperm two cells of equal size. in the production of egg cells cytokinesis is asymmetric and produces one large cell that undergoes meiosis II and the other cell is a polar body and will not undergo meiosis II and will not produce gametes
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Why does no replication occur between the end of meiosis I and the beginning of meiosis II
the chromosomes are already replicated
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What does not occur in prophase II
synapsis does not occur
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What is the result at the end of telophase II and cytokinesis?
each daughter cell is genetically distinct from the others and from the parent cell. four sperm cells are formed, one large egg, and a second polar body
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When comparing mitosis and meiosis: mitosis
conserves the number of chromosome sets producing cells that are genetically identical to the parent cell
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When comparing mitosis and meiosis: meiosis
reduces the number of chromosomes sets from two (diploid) to one (haploid), producing cells that differ genetically from each other and from the parent cell
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What contributes to genetic variation?
Crossing over Independent assortment of chromosomes Random fertilization
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What allows for independent assortment of chromosomes?
homologous pairs of chromosomes orienting randomly at metaphase I
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Each pair of chromosomes do what in relation to independent assortment?
sorts maternal and paternal homologs into daughter cells independently of the other pairs
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What did Mendal focus on
independent assortment of alleles of a particular gene not a whole chromosome
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What is the multiplication rule and how is it used
used to determine when two or more independent events will occur together the probability is the product of their individual probabilities
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What is the addition rule?
probability that any one of two or more exclusive events will occur is calculated by adding together their individual probabilities
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genes on the X chromosome are
X-linked
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genes on the Y chromosome are
Y linked
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what needs to occur for a recessive X-linked trait to be expressed in a female versus a male
female 2 copies; male 1