Cell cycle

Question 1

Define cell cycle

Answer 1

ordered series of events tha lead to cell division and produciton of 2 daughter cells

Question 2

What happens in each step of cell cycle

Answer 2

G1 - DNA is preparing to divide, goes to S if DNA is intact and enough resources
G0 - resting- none dividing phase, exits the cell cycle
S - where the cell replicates DNA, goes to G2 if no errors in replication
G2 - continued growth, prepare for division, needs to have intact DNA, all chromosomes and cell components to go to M
M - where the cell divides

Question 3

What are 3 fates in cell cycle

Answer 3

Cell division - cell makes identical daughter cells in response to molecular signals such as growth factors
Differentiation - when cells stop dividing to specialize in structure and function. Some of them can’t re enter cell cycle
Apoptosis- when cells die because they are old or unhealthy, if the cell genome has been damaged or for development

Question 4

Under what conditions does cell enter g0

Answer 4

1. When it receives a signal to differentiate
   
   2. there is not enough nutrients to grow, or growth factors (called mitogens, signals to divide )

Question 5

What cells never re enter cell cycle

Answer 5

Neurons and muscle cells never re enter the cell cycle*

Question 6

consequences of abnormal cell cycle

Answer 6

anueploidy/polyploidy - unequal chromosome sep
Tumor formation - if turn off tumor supressor + turn on proto oncogenes

Question 7

what is WNT signal pathway for, why important

Answer 7

regulates proliferation, cell growth,
found in intesting to maintain stem cell niche
if it is defective the cell divide uncontrollably

Question 8

at what stage to cells replicate DNA

Answer 8

S, also where DNA is checked for errors

Question 9

What is CDK (when is it used, why is it good)

Answer 9

CDK- most important cell cycle regulators, kinases. we don’t want them active allt eh time
Activating CDK- cycling stimulates cell cycle, makes sure DNA is normal
G1 - push cell cycle to S phase when growth factors cause cycling concentrations to rise and activate CDK
S - CDK cyclin stimulate cell to reduplicate DNA

Its activated when it binds to cyclin. CDK is present all the time, cyclin is not
Kinases are proteins that phosphorylate
The phosphate can activate or deactivate target .

Question 10

How does cyclin, CAK, Cdc25 regulate CDK

Answer 10

CDK has T loop which blocks atp
the cyclin A induces confromational change in CDK and moves the T loop slightly out of the way - makes it low activity
sometimes it also requires cyclin acivated kinase to phosphorylate the t loop and make CDK even more active.
Cdc25 - dephosphorylates other parts of CDK that are inhibitory

Question 11

Cyclin dependant kinase vs cyclin vs cdk activating kinase

Answer 11

cyclin dependant kinase (CDK) - catalytic subunit - intrinsically inactive, due to t loop that naturally blocks atp pocket
cyclin - regulates CDK and other things, conct cycles throughout cell cycle, exposes active site in CDK, making it more active
CDK activating kinase (CAK) - phosphorylates thr160 in CDK, fully activates CDK, happens after cyclin bonding

Question 12

What is p 53 and where does it work

Answer 12

P53 - tumor suppressor, responsible for regulating cell cycle. Inhiits cell cycle genes. Activates expression of DNA repair genes, apoptosis.
Overall funciton is to supress cell cycle progression. Used in G1 (to see if DNA is damaged), G2 (stops cell cycle if DNA is damaged).

Question 13

How is cyclin d regulated

when is it found

Answer 13

With growth factors, mitogens
expressed only when mitogens are present, peaks around late G1in restriciton point
Cyclin b is used in G2
Cyclin A and E used in G1/S transition if no DNA problems

Question 14

What does cyclin d do

Answer 14

phosphorylates and inactivate teh cell cycle inhibitor retinoblastoma which is binded to E2F
once RB is phosphorylated it no longer binds to E2F which stops acting like inhibitor

Question 15

Main points in G1 phase

Answer 15

longest phase
checks if env is good, checks if it got growth factor stim,
has 2 checkpoints
1. Restriction point - gateway in late G1 regulates expression of genes needed for cell cycle, looks for tumor supressor (retinoblastoma) and E2F transcription factors
once it passes restriction point its commited to S phase
2. G1/S checkpoint looks for DNA damage

Question 16

main DNA damage sensors in G1/S

Answer 16

G1/S is checpoint in late G1 phase to look for DNA damage
Ataxia telangiectasi mutated (ATM) - ser-thr kinaserecognizes double stranded breaks
ATR - ser/thr kinase, recognizes damage associiated with DNA SSB and DSB

Question 17

What happens if there is damage found at G1/S phase

Answer 17

DSB signals ATM to be phosphoorylated. ATM is kinase.
then E2F is phosphorylated, activate apoptosis genes
also enhances P53 which increases apoptosis genes
P53 increases expression of P21 which is trans factor, inhibits CDK, prevents cell cycle cont
Mdm2 is also phos and inactivated. and no longer suppresses p53

If there is SSB then ATR is activated and phosphrylates other kinase, CHK1
This then phos and inhibits CDC 25.
This signals to cell to degrade it and suppress cell cycle

Question 18

what happens if no damage found in G1/S transition (what cyclin is present, no wee1)

Answer 18

Cyclin E/CDK2 and cyclind A/CDK2 increases - more phorphorylation of pRetinoblastoma (further stops it from inhibitind creation of cyclin E/A, CDK1, cdc25), cells got to S phase
pRB is phosphorylataed thorugh s g2 and M

Question 19

What does E2F do

Answer 19

is inhibited by RB
acts as transcription factor, activates transcription of genes needed for S phase
activates Cyclin E, A, Cdk1 and cdc 25

Question 20

What happens in S phase

mcm2-7, ORC how is it triggered

Answer 20

dna replication
cyclin A/E and CDK triggers ORCs
org of replication complexes start (ORCs)
CDK activates MCM2-7 : a helicase- unwinds DNA
Dna is replicated
high lvls of CDK prevent more replication by binding to ORC

Question 21

What happens in G2 (what does cyclinA / CDK do, Wee1, condense complex)

Answer 21

does final check for DNA damage from replication
organelles are duplicaed

CyclinA/CDK1 initiate spindle pole formation, phos the condensin protien complex - causes chromatin to condense
Wee1 - binds to CDK1 and prevents premature mitosis, so cycling can accumulate

Question 22

What happens if DNA is intact vs damaged in G2

Answer 22

intact
- CDC25 removes inhibitory phosphate on CDK1
-Wee1 is deactivated
-cyclin B - CDK1 drives mitosis
Damaged
- atm/Atr response
- cycling A/CDK1 and Cyclin b/CDK1 stay inactive
-Wee1 stays active, inhibits CDC25 which would usually dephos the CDK and activate it
- cell repairs or dies

Question 23

What happens if CDK is inhibited like in ATM

Answer 23

RB stays unphosphorylated (keeps binding to E2f, would usually be phos all the way through cell cycel starting in G1)
E2F remains inhibited (phosphorylation of RB activates E2F)

Question 24

What does CAK, Wee1, CDC25 A/C, RB, P21do

Answer 24

CAK - activates CDKs
Wee1 inhibits CDK
Cdc 25A - activates S phase CDKs
cdc25C - activates mitotic CDKs
rb - binds to E2F, prevents transcription of cyclin, cdks and other cell cycle genes
p21- binds and inhibits CDKs

Question 25

Chain in healthy vs unhealthy cell (Start at GF and ATM/ATR)

Answer 25

Healthy growth fact -> promote cyclin D/CDK4/6 ->phos RB -> no longer inhibits E2F-> makes cyclin E/A-> pushes to Sphase-> makes cyclin B/C CDK1-> pushes to mitosis NOT Healthy ATM/ATR - > activates p53 - > promotes p21 -> inhibits CDK-> stops cell cycle bc RB stays unphos-> repair or apoptosis

Question 26

how to know when which cyclin is used and with which CDK (4 CDKs, 6 cyclins)

Answer 26

cyclin start at G1 phase with D, CDK start at G1 with 6,4, uses Cyclin D CDK 2 is used with cyclin E, A in S phase and G1/S CDK1 with Cyclin A, B in mitosis CDK1 + cyclin A at G2

Question 27

is cyclin, RB, CDK usually amplified or supresses in cancers

Answer 27

Cyclin is amplified RB is supressed CDK is amplified

Question 28

What are steps of cell cycle

Answer 28

interphase + mitosis interphase = 4 steps (G0, G1, S, G2) Mitoses = 5 steps (prophase, metaphase, anaphase, telophas, cytokinesis)