Module 6 Flashcards
(76 cards)
1
Q
four phases of the cell cycle
A
G1, S, G2, M
2
Q
G1 phase
A
- first gap
- cells grow in size and synthesize RNAs and proteins required for DNA synthesis
- cell evaluates its status and determines whether to commit to cell division and doubling
- evaluating cell size, nutrient status, substrate attachment, density of neighboring cells, and the presence of extracellular growth factors/chemicals that stimulate cell division
3
Q
S phase
A
- synthesis
- chromosomes are replicated
- once the cell enters S phase it has to duplicate its chromosomes and can not go back
- replication machinery is assembled at specific sites on the chromosomal DNA at the origins of replication
- centrosome (microtubule organizing center) also duplicates
4
Q
G2 phase
A
- second gap
- making sure chromosomes have been replicated properly
- errors made during DNA copying are corrected
- breaks in the DNA strands are repaired
- first signs of chromosome condensation occur
- early reorganization of the cytoskeleton and microtubules
- preparing for mitosis
5
Q
M phase
A
- mitotic phase
- cell divides
6
Q
chromatid
A
- one copy of a replicated chromosome
- joined to sister chromatid (other copy)
7
Q
cohesin
A
- protein complex that holds sister chromatids together
- dissolves during mitosis before separation of sister chromatids
8
Q
centromere
A
- central region of chromosome
- where kinetochore forms
- appears constricted
9
Q
prophase
A
- chromosomes condense and become visible
- centrosomes move toward opposite poles and spindle begins to form
- cohesin is shed from chromosome arms
- kinetochore assembles on centromere
10
Q
prometaphase (higher eukaryotes)
A
- chromosomes continue to condense
- mitotic spindle microtubules attach to kinetochores
- nuclear envelope breaks down
- non-kinetochore microtubules reach across the cell to overlap with those arising from the other centrosome
11
Q
metaphase
A
- chromosomes are lined up at the metaphase plate
- each sister chromatid is attached to a spindle fiber originating from opposite poles
12
Q
anaphase A
A
- cohesin glue that held sister chromatids together at the kinetochores is dissolved
- individual sister chromatids separate from one another and move towards opposite poles of the spindle as the kinetochore microtubules shorten
13
Q
anaphase B
A
non-kinetochore microtubules lengthen, causing the cell to elongate as the spindle poles separate further
14
Q
telophase
A
- chromosomes arrive at opposite poles and begin to decondense
- nuclear envelope starts to reform and nucleoli reappear
- mitotic spindle breakdown
- contractile ring assembles under plasma membrane (in animal cells)
15
Q
cytokinesis
A
- cytoplasm is divided between the two daughter cells
- involves formation of a cleavage furrow by narrowing the contractile ring and severing remaining microtubules in between the two daughter cells
- forms two discrete cells each containing a nucleus, cytoplasm, and other structures present in the mother cell
16
Q
cyclin dependent kinases (CDKs)
A
- control the cell cycle by phosphorylating substrates that when properly phosphorylated directly cause the events in each cell cycle stage to take place
- need cyclin to be activated
- a serine and threonine kinase (phosphorylates serine and threonine residues)
17
Q
mitosis promoting factor (MPF)
A
a dimer made up of CDK and cyclin
18
Q
How do CDKs control the cell cycle?
A
- cyclins are synthesized and degraded by proteasomes in a cyclic manner
- CDK levels remain the same throughout the cell cycle
- presence or absence of specific cyclin makes the CDKs inactive and active
19
Q
What are the different types of CDKs?
A
- G1
- G1/S
- S
- Mitotic
20
Q
G1 cyclin-CDKs
A
- promote entry into the cell cycle
- cyclin D/CDK4/6
- cyclinE/CDK2
- phosphorylate RB so that E2F transcription factor is active and can bind to the upstream region of genes and initiates gene expression
21
Q
RB
A
- retinoblastoma
- binds to E2F (transcription factor)
- when bound to E2F, E2F is inactive
22
Q
E2F
A
- transcription factor
- when bound to RB it is inactive
- when RB is phosphorylated, it is active
- increases gene expression of other genes and itself
- increases gene expression of cyclin E (G1 cyclin)
23
Q
retinoblastoma
A
- cancer of the retina
- have mutated nonfunctional RB
- E2F is always on (does not halt the cell cycle at G1/S transition resulting in uncontrolled cell division
24
Q
Sic1
A
- S-phase cyclin inhibitor
- makes sure that S-phase cyclin-CDKs are not active during G1
- G1 cyclin CDKs phosphorylate Sic1, causing it to be a target for ubiquitination
- addition of ubiquitin groups marks Sic1 for degradation by a proteasome
25
S phase cyclin-CDKs
- pre-replication complexes assemble at the origins of replication during G1
- when you get S-phase cyclin-CDK, it will phosphorylate the proteins in the origin recognition complex
- DNA begins to unwind and phosphorylation groups are added directly to the components of the replication origin which activates them -> inducing DNA replication
- trigger S phase
26
Unreplicated-DNA checkpoint
- end of G2 before M phase
- checking to make sure that all DNA was replicated properly in S phase
- if DNA is not replicated ATR is activated which activates Chk1 which inhibits Cdc25c
- Cdc25c is responsible for activating the cyclin that mediates G2 to M phase entry
27
ATR
- activates Chk1
- unreplicated DNA checkpoint
- activated when DNA is not replicated properly
28
Chk1
- inhibits Cdc25c
- activated by ATR
- unreplicated DNA checkpoint
29
Cdc25c
- activates cyclin that mediates G2 to M phase entry (Cyclin A/B CDK1)
- inhibited by Chk1
- unreplicated DNA checkpoint
30
Spindle assembly checkpoint
- checking whether the spindle formed properly and whether all chromosomes are lined at the center
- if not, Mad2 is activated which inhibits APC-Cdc20 (proteasome responsible for degrading securin)
- when securin is not degraded, the sister chromatids can not come apart
- cell will not enter anaphase
31
Mad2
- inhibits APC-Cdc20 (proteasome)
- activated in the spindle assembly checkpoint if the spindle is not formed properly or the chromosomes are not aligned in the center
32
APC-Cdc20
- proteasome that degrades securin
- inhibited by Mad2
- when inhibited, prevents sister chromatids from separating and therefore anaphase from happening
- spindle assembly checkpoint
33
Chromosome segregation checkpoint
-happens right before telophase
-makes sure that chromosomes are segregated to the poles properly
-if not, Cdc14 (responsible for activating APC-Cdh1, a proteasome complex that degrades and ubiquitinates mitotic cyclins) is inhibited
-prevents cell from entering telophase if there isn't proper segregation
-
34
DNA damage checkpoint 4a
- seeing if there was DNA damage during G1
| - ATM/R activates p53-> induces expression of p21CIP -> inhibits cyclin D/CDK4/6 (G1 cyclin)
35
DNA damage checkpoint 4b
- checks for DNA damage before entering S phase
- AMT/R activates p53 ->induces expression of p21CIP -> inhibits Cyclin E/A-CDK2 (S phase cyclin)
- ATM/R activates Chk1/2-> inhibits Cdc25a-> would normally activate S phase cyclin
36
DNA damage checkpoint 4c
- checking for DNA damage in S phase
- ATM/R activates p53 -> induces expression of p21 CIP -> inhibits Cyclin A-CDK2 (S phase cyclin)
- ATM/R activates Chk1/2 -> inhibits Cdc25a which would normally activate S phase cyclins
37
DNA damage checkpoint 4d
- checks for damage during G2
| - ATR activates p53 -> induces expression of p21CIP -> inhibits Cyclin A/B-CDK 1 (G2 phase cyclin)
38
ATM/R
activates Chk1/2 and p53
39
p53
- the guardian of the genome
- activated by ATM/R
- induces expression of p21 CIP
40
p21 CIP
inhibits cyclin CDK dimers (halts the cell cycle)
41
Cdc14
- chromosome segregation checkpoint
- activates APC-Cdh1 which degrades and ubiquitinates mitotic cyclins
- inhibited when chromosomes are not segregated properly
42
Cdc25a
- normally activates S phase cyclins
| - is inhibited by Chk1/2
43
Who won the Nobel Prize for Physiology and Medicine in 2012?
- Shinya Yamanka and John Gurdon
| - advanced the field of stem cell research
44
Shinya Yamanka
- demonstrated that there were 4 genes whose expression was critical to giving an embryonic stem cell its phenotype or "nature"
- those genes are OTC3/4, Sox2, klf4, and c-MYC
- successfully turned adult cells into embryonic stem cells
- cells produced by this technology are called IPSCs (induced pluripotent stem cells)
45
John Gurdon
- pioneered somatic cell nuclear transfer
| - cloned frogs using this technique
46
properties of stem cells
- can propagate themselves
| - can be differentiated (can also go back to being a stem cell)
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unipotent stem cell
can form only one type of differentiated cell
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multipotent stem cell
can form multiple differentiated cells
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pluripotent stem cell
can form all of the 200 differentiated cells
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totipotent stem cell
can form all of the differentiated cells plus specialized tissues (ex: placenta)
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multipotent hematopoietic stem cell (HSC)
divides into common myeloid progenitor and common lymphoid progenitor
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common lymphoid progenitor
makes T cells and B cells of the immune system
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common myeloid progenitor
- granulocytes
- monocytes
- eosinophils
- erythrocytes
- megakaryocytes
54
LGR5+ stem cells
- leucine rich G-protein coupled receptor 5
- receptors are a biomarker of LGR5+ cells (only expressed in these stem cells)
- can turn into any cell
55
+4 stem cells
- occupy 4th position from the crypt base
- are generated from LGR5+ cells
- can restore LGR5+ cells following injury
56
transient amplifying cells
- divide to produce the variety of differentiating cells (enterocytes, tuft cells, Goblet cells, enteroendocrine cells)
- migrate up
57
paneth cells
- regenerated from transient amplifying cells
| - migrate to the base of the crypt and secrete antimicrobial defense proteins
58
embryonic carcinoma cells
- derived from tumors that arise in germline cells (sperm and egg)
- develop when a sperm or egg cell loses cell cycle control
59
benign embryonic carcinoma tumor
teratoma
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malignant embryonic carcinoma tumor
teratocarcinoma
61
testicular teratocarcinoma
- grows hair
| - malignant tumor in sperm
62
ovarian teratocarcinoma
- grows teeth
| - malignant tumor in egg cell
63
somatic cell nuclear transfer
- aka cloning
- oocyte is enucleated (nucleus is removed)
- nucleus from adult cell is transferred into the oocyte to form a nuclear transfer embryo (2n)
- embryo becomes blastocyst
- blastocyst is transferred into the uterus of a surrogate mother
- final result is a clone
64
kinetochore microtubules
microtubules that are interacting with the chromosomes
65
polar microtubules
microtubules that don't interact with chromosomes, but interact with each other in the center of the spindle
66
astral microtubules
form tufts at either end of the mitotic apparatus
67
bi-orientation
- chromosome is attached to one kinetochore microtubule emanating from one spindle pole and another kinetochore microtubule emanating from the other spindle pole
- failure to get in bi-orientation can result in aneuploidy
68
chromosome capture and congression in prometaphase
1. kinetochores can attach to the kinetochore microtubule via end capture or side capture
2. chromosome is drawn to the spindle pole by dynein-dynactin motor protein complex associated with one of the kinetochores walking toward the minus end of the kinetochore microtubule
3. a kinetochore microtubule from the opposite pole becomes attached to the free kinetochore to bi-orient the chromosome
4. chromosomes with only one kinetochore pole interact with kinesin 7 (aka CENP-E)
5. congression (tug of war)
5a. on the shortening side, kinesin 13 stimulates kinetochore microtubule disassembly at the + end
5b. on the lengthening side, kinesin 7 holds onto the growing microtubule
5c. kinesin 4 (chromokinesin) holds the chromosome arms facing away from the spindle poles
69
kinesin 13
stimulates kinetochore microtubule disassembly at the plus end on the shortening side
70
kinesin 7
holds on to the growing microtubule on the lengthening side
71
kinesin 4
- keeps chromosome arms facing away from the spindle poles
| - chromokinesin
72
CENP-A
- variation of histone 3 that is found at the kinetochore region of chromosomes
- marks the kinetochore for the mitotic apparatus
73
Ndc80
- Ndc (nuclear division cycle)
- interacts with the microtubule on one end and the inner kinetochore on the other end
- forms a tension
- connects microtubule to chromosome
74
CPC
- chromosome passenger complex
- contains Aurora B kinase
- Aurora B kinase phosphorylates Ndc80 making its microtubule association weak
- in bi-orientation, Aurora B kinase can not phosphorylate Ndc80 so Ndc80 becomes very tightly associated with the microtubule
75
spindle elongation in anaphase B
- kinesin motors are attached to two different polar MTs and their heads try to walk toward the plus end of the MT
- polar MTs are pushed in opposite directions
- eventual polymerization of new MT at + end as they stretch
76
cell elongation in late anaphase and telophase
- astral microtubules interact with dyneins
- the tail of the dyneins are bound tightly to the plasma membrane
- heads of dyneins walk towards the minus end
- causes a tension that pulls on the astral MTs so that you get further elongation
