Flashcards in The Nucleus Deck (91):
1
Function of the nucleus
1. Replicate dna
2. Synthesized and produce all types of rna
3. During interphase pore complexes in nuclear membrane regulate Macromolecular transfer between nucleus and cytoplasm
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Why is protein synthesis restricted to the Cytoplasm
helps ensure that newly made rna molecules do not become involved in translation before processing is complete
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Component of nucleus
1. Nuclear envelope
2. Chromatin
3. Nucleoli
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Chromatin
Mass of DNA and its associated Proteins
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Nucleoli
Specialised regions of Chromatin
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Characteristics of nuclear envelope
1. Selectively permeable membrane
2. 2 concentric membranes adulterated by perinuclear space
3.space and outer membrane Continuous with RER
4. Nuclear lamina associated inner membrane
5. Nuclear pore complex
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Perinuclear space
Space between outer and inner nuclear membrane 30-50nm. Space is continuous with cytoplasmic network of RER
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Nuclear lamina
Highly organized mesh work of proteins associated with the inner nuclear membrane.
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Function of nuclear lamina
Stabilizes the nuclear envelope
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Component of the nuclear lamina
Components are a class of intermediate filament protein called lamina. That bind to membrane proteins and associated with Chromatin in non dividing cells
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Structure of nuclear protein
1. Bridge the inner and outer nuclear membrane
2. Made of Core proteins called nulceoporins
3. Display 8-fold symmetry around lumen
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Function of pore complex
Regulate movement of Macromolecules.
Growing cells contain, 3000-4000 such channels providing passage for upto 1000 molecules per second
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Macromolecules moved out of the nucleus
1. Ribosomal subunits
2. RNA associated with proteins
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Macromolecules transferred into the nucleus
1. Ribosomal protein
2. Transcription factors
3. Chromatin protein
4. Enzymes
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Mechanism for transportation of Macromolecules into and out of the nucleus
1.Protein complexes transported to cytoplasm have specific nuclear export sequences
2. Proteins to be imported have nuclear localization sequences
Both bind to specific transport proteins that interact with proteins of pore complex for transfer across across nuclear envelope. Energy derived from GTP with specific GTPase help provide directionality to the transfer.
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Types of transport protein
Important, exportins, etc
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Cells Chromatin divided into___ no. Of chromosomes
46 (23pairs)
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After DNA replication but before cell division chromosomes contain identical Chromatin units called
Chromatids held together by complexes of cohesin protein at the centromere
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Length of the DNA
2m long with 3.2 billion base pairs
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What is a histone
Small basic protein
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What is a histone
Small basic protein
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Nucleosome
It is a structural unit made of a core of 8 histone around which is wrapped about 150bp of DNA.
Gives a "beads on a string" appearance with 50-80bp of linker DNA separating each Nucleosome
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H1 histone
Each Nucleosome has a large histone H1 associated with both the wrapped DNA and the surface of the core.
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Why are Nucleosomes structurally dynamic
Because they can undergo modifications and rearrangement of the histones to allow temporary unwrapping of DNA and arrival of enzymes and other protein required for replication and gene Transcription.
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Stages of DNA wrapping
1. 2m DNA wrap around histones forming Nucleosomes diameter of 11nm
2. Nucleosome undergo helical folding yield fiber of diameter 30nm
3. formation of transcriptionally active
DNA (euchromatin) into loops that are tethered to a central scaffold of proteins that include the
condensing.
4. Formation of chromosomes
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Function of condensins
Part of Central scaffold and promote compaction of Chromatin
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two types of Chromatin
1. Heterochromatin
2. Euchromatin
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appearance of Heterochromatin under an EM and light microscope
coarse, electron-dense material in the electron microscope and as intensely basophilic clumps in the light microscope.
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appearance of Euchromatin under light and electron microscope
visible as finely dispersed granular material in the electron microscope and as lightly stained basophilic areas in the light microscope.
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difference between Heterochromatin and Euchromatin
Heterochromatin Euchromatin
1.Tightly coiled 1.loosely packed
2. Darkly stained 2. Lightly stained
3. Little or no 3.Transcriptional
Transcription active
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function of the nucleus
1.Cellular Regulations: houses genetic material, directs cell activities, regulates cell structure
2.production : produces Ribosomal subunits in the Nucleolus
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The inner and outer nuclear membranes are bridged at
nuclear pore complexes
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2 types of Heterochromatin
Constitutive Heterochromatin
Facultative Heterochromatin
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Constitutive Heterochromatin
Contains mainly repetitive gene- poor DNA sequence
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Chromosomal regions of Constitutive Heterochromatin
Centromere abs telomeres located near the middle and ends of the chromosome respectively
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Facultative Heterochromatin
Contains regions of DNA with genes where Transcription is variable inactive by epigenetic mechanism.
Can undergo reversible transition from compact transcriptionally silent state to more open transcriptionally active confirmations
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Indicator of cells metabolic and biosynthetic activity
Ratio of Heterochromatin to Euchromatin-Euchromatin predominates in active cells ex. Large neuron, while Heterochromatin is abundant in cells with little synthetic activity ex. Lymphocytes
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Barr body
One of the 2 X chromosomes present in human females but not males. Made of Facultative Heterochromatin it remains tightly coiled while the other X chromosome is uncoiled.
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X chromosome is males
Remains largely Euchromatic
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Chromosomal territories
When sequences on each individual chromosomes are labeled differently with florescent probes, each structure occupies a discrete Chromosomal territory
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Why are memers on each Chromosomal pair called homologous
Although they come from different parents they contain alleles of the same gene
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How is microscopic analysis of chromosomes done
Begins with cultured cells arrested in mitotic metaphase by colchicine or other compounds that disrupt microtubules. After processing and staining the cell the condensed chromosomes are photographed by a light microscopy and rearranged digitally to produce a karyotype in such Stained chromosomes can be analyzed
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Medical application of Barr bodies
1.Permit gender to be determined microscopically in patients whose external sex Organs do not permit determination ex. In hermaphroditism and pseudohermaphroditism
2. Reveals other anomalies involving the sex chromosome ex. Klinefelters syndrome
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Medical application of karyotyping
1. Prenatal diagnosis - detect certain genetic anomalies
2. In adults - missing or extra chromosomes and Chromosomal deletions or translocations easily seen
45
Characteristic of a Nucleolus
1. Spherical
2. Highly basophilic
3. In nuclei of cells actively engaged in protein synthesis
4. rRna production and ribosome assembly
5. Contains fibrillar and granular subregions
46
Intense basophilia of nucleoli is due to
Densely concenrated rRNA that is transcribed processed and assembled into Ribosomal subunits
47
What is neoplastic profileration
Cells become transformed to grow at a higher rate and in an uncoordinated manner
48
Cause of neoplastic profileration
Damage to the DNA of proto-oncogenes and failure of cells to be eliminated.
49
Laminopathies
Mutation in the gene coding for particular lamin. Nuclear envelope is abnormal.
50
Progeria disorder
Mutation in the gene coding for lamin A. Causes Premature aging
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Cell cycle
Regular sequence of events that produce new cells
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Phases of cell cycle
1. Mitosis
2. G1
3. S
4. G2
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G1 phase
1.Period between mitosis and beginning of DNA replication. Longest and most variables
2. Active RNA and protein synthesis
3. Cells volume, reduced by half during mitosis, return to its pervious size
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S phase
1.Period of DNA synthesis- DNA replication
2. Histone synthesis
3. Centrosome duplication
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G2 phase
1. Gap between DNA Duplication and the next mitosis
2. Proteins required accumulated
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G0 phase
New postmitotic cells specialize and differentiate, cell activities may be temporarily or permanently suspended.
Some differentiated cells like liver cells renew cycling under certain conditions, while others like most muscle and nerve cells are terminally differentiated.
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How is cycling activated in the postmitotic G0 cells
Activated by protein signals from the extracellular environment called mitogens or growth factors which attach to cell surface receptors and trigger a cascade of kinase signaling in the cells. Then maintained at the restriction point at G1/S boundary until sufficient nutrients and enzymes required for DNA synthesis have accumulated, once all is ready S phase begins
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Checkpoints of cell cycle
Entry and progression through other phases of the cycle are monitored at these points, where certain condition must be met before the cell continues cycling.
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Cell cycling is regulated by
A family is cytoplasmic proteins called cyclin
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How do Cyclin proteins regulate cells cycle
Different Cyclin for different cell cycle phase each activate one or more specific Cyclin-dependent kinase (CDKs). Activated CDKs then phosphorylates specific proteins including enzymes, Transcription factors for specific genes and cytoskeletal subunits, triggering the activities that characterize the next phase of the cycle. Once each successive set of activities is completed the Cyclin controlling that phase is removed by proteasomes and a new Cyclin that promotes the activities of for the next phase takes over.
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Commercially produced mitogens growth factors
Analogs of granulocyte colony-stimulating factor (G-CSF)
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Three important checkpoints
1.The start or restriction checkpoint just before the start of S- G1/S
2. The G2/M checkpoint that ensures that DNA replication is complete
3.The metaphase spindle checkpoint that ensures that all chromosomes will be segregated- metaphase/anaphase checkpoint
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DNA changes (mutations) resulting from damage detected by
tumor suppressor proteins such as p53. many forms of human cancer, the gene for the key tumor suppressor p53 is itself mutated, thus reducing the ability to eliminate cells with damaged DNA and facilitating proliferation of cells with new genetic defect.
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Retinoblastoma
is a type of cancer occurring in the eyes, usually in young children.
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Rb gene
codes for a key protein active at the G1
restriction point that blocks cell cycle
progression until a mitogenic stimulus arrives. A kinase activated by a growth factor receptor
phosphorylates the Rb protein, causing it to release the E2F transcription factor. This factor then activates genes needed for DNA replication.
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What causes cell cycle to halt
By adverse conditions such as inadequate nutrition, inappropriate cellular microenvironment, or DNA damage
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Function of G-CSF
Stimulates neutrophil production in immunocompromised patients and erythropoietin, which can stimulate red blood cell formation in patients with anemia
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When there is DNA damage where is the cell cycle stopped
It can be arrested at G1 restriction point, S or G2 checkpoint
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What happens if dna damage encountered at check point cannot be corrected while cycle is halted
Protein enclosed by tumor suppressor gene such as p53 are activated and cells activity get redirected towards apoptosis
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Protogenes
Genes coding for proteins that control cell profileration and Differentiation. They encode almost any protein involved in the control of mitotic activity
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Oncogene
Change in structure or expression of a proto-oncogene convert them into oncogenes that cause uncontrolled cell growth and potential for cancer
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Morphologically distinct regions within the Nucleolus
1. Light staining fibrillar centers - contain DNA with the rRNA genes
2. Darker fibrillar material - accumulating rRNA transcripts
3. Granular Material- larger and smaller Ribosomal subunits being assembled
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Function of E2F Transcription factors
Activates genes needed for DNA replication
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Mitosis
Present cell divides and each of the 2 daughter cells receive a Chromosomal set identical to that of the parents cell
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Long period began mitosis
Interphase - G1, S and G2 phases
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Prophase
1.Longest
2. Nucleolus disappears
3. Chromosome with sister chromatids are condensed
4. Duplicated centrioles separate to opposite poles and organize microtubules of mitotic spindle
5.lamin and nuclear membrane phosphorylated causing them to disassemble
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Metaphase
1. Chromosome condensed further
2. Kinetochores attach to the mitotic spindle
3. Cell is more Spherical
4. Chromosome moved into alignment at the equatorial plate
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Anaphase
sister chromatids separate move toward opposite poles
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Telophase
1. 2 sets of chromosomes are at the poles
2. Chromosomes decondense
3. Spindle depolymerizes
4. Nuclear envelope reassembles around each daughter chromosome
5. Contractile ring of actin filaments develops in cortical cytoplasm at the cells equator to produce cytokinesis
80
Duration of cell cycle
Varies from 24-36 hours. G1 depends on many factors usually the longest memoir variable 25h, S depends on genomic size, G2 and mitosis together last only 2-3hs
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capacity for mitosis within a tissue, either by differentiated cells or by reserve
cells, largely determines that tissue’s potential to
regeneration
82
Kinetochores microtubules
Polar microtubules which interdigitate near the equatorial plate
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Astral microtubules
Anchoring the spindle to cell membrane
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Stem cells
1.Undifferentiated cells whose cycling serves to renew the differentiated cells of tissue.
2.Divide infrequently
3.Division is asymmetrical - one daughter cell remain as a stem cell, the other leads to Differentiation
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Where are stem cells found
In specific locations or niches where the microenvironment helps maintain their uniquely undifferentiated properties
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Progenitor cells
Aka transit amplifying cells are in transit asking the path from the stem cell niche to a differentiated state, and amplifying by mitosis the number of new cells available for the differentiated tissue
87
Meiosis occurs in
Cells that will form spiel and egg cells
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2 key features of Meiosis
1. Synapsis and crossovers
2. Produces haploid cells
89
Events in Meiosis
1. Completes S phase, replicated it's DNA, chromosome contains 2identical DNA molecule called sister chromatids
2. Prophase I partially condensed Chromatin of homologous chromosome undergo Synapsis and refered to as tetrads
3.crossing over occurs
4. Chromosome fully condense undergo metaphase, anaphase, and telophase separating the homologous chromosomes
5. New cells divide again rapidly without S phase
6. meiosis II separation of chromatids form new haploid set of chromosomes
90
Difference between mitosis and Meiosis
1.Mitosis produces 2 diploid cells, Meiosis involves 2 cell division and produce 4 haploid cells
2. In Meiosis every haploid cell is genetically unique, mitosis yield 2 cells that are the same genetical
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