Continued cell proliferation

Question 1

cyclins

Answer 1

proteins control progression of cells through the cell cycle

Question 2

cyclins in G1

Answer 2

cyclin D
bind to CDK4 and CDKGH

Question 3

cyclins in late G1

Answer 3

cyclin E
bind to CDK2

Question 4

cyclins in S phase

Answer 4

cyclin A
bind to CDK2

Question 5

cyclins in G2

Answer 5

cyclin A
bind to CDK1

Question 6

cyclins in M

Answer 6

cyclin B
bind to CDK1

Question 7

what does CDK mean

Answer 7

cyclin dependent kinases
they phosphorylate serine and threonine residues on target proteins

Question 8

members of cyclin D

Answer 8

D1-3

Question 9

members of cyclin E

Answer 9

E1 and E2

Question 10

members of cyclin A

Answer 10

A1 and A2

Question 11

members of cyclin B

Answer 11

B1-3

Question 12

what is occurring in the image

Answer 12

CDK is inactive
T loop obscures the active site
no ATP binding

Question 13

what is occurring in the image

Answer 13

binding of cyclin changes the T loop conformation
partial CDK activation

Question 14

what is occurring in this image

Answer 14

full CDK activation
by T loop phosphorylation by CDK activating kinase CAK
enables optimum ATP binding

Question 15

how is active CDK inactivated

Answer 15

by Wee kinase
inhibitory phosphorylation

Question 16

how is inhibitory phosphorylation on CDK reversed

Answer 16

by CDC25 family of phosphatases

Question 17

G1 to S transition mechanism

Answer 17

mitogen signalling activate Myc
Myc activates transcription of cyclin D
cyclin D binds and activates CDK4/6
CDK4/6 phosphorylates Rb which inactivates and causes it to release its inhibition on E2F1
E2F1 induces gene expression of cyclin E
cyclin E/CDK2 hyper phosphorylates Rb and completely inactivates it
E2F1 also induces expression of cyclin A required in S phase

Question 18

S phase

Answer 18

activation of helices by CDK2/cyclin A starts DNA replication
components of preRC are phosphorylated preventing them rebinding to DNA and relicensing the replication complex

Question 19

G2 phase

Answer 19

activating CDK1/cyclin B required for mitosis
1. CDK1/cyclin A activates CDC25 phosphatase, removes inhibitory phosphate on CDK1/cyclin B complex
2. Active CDK1/cyclin B: inactivates Wee1 via phosphorylation, activates CDC25 via phosphorylation (positive feedback)

Question 20

M phase

Answer 20

CDK1/cyclin B phosphorylates and activates condensin, compacts DNA by folding and coiling
CDK1/cyclin B phosphorylates proteins of the nuclear envelope so they disassemble
CDK1/cyclin B activates centrosomes, move apart and increase microtubule length

Question 21

what are the stimuli for cell cycle checkpoints (DNA damage)

Answer 21

microtubule spindle defects
unreplicated DNA
lack of growth factors
chromosomal deregulation
excessive mitogenic signalling

Question 22

CDK inhibitor proteins

Answer 22

bind cyclin and CDK, distort CDK active site
CKI’s insert into the ATP binding site, inhibits CDK enzymatic activity
2 main groups called INK4A family and CIP/WIP family

Question 23

members of INK4A family

Answer 23

p16^INK4A
p14^ARF

Question 24

members of CIP/WIP family

Answer 24

p27^KIP1
p21^CIP1

Question 25

proto-oncogenes

Answer 25

pro cell division cyclins CDKs E2F1 CDC25 deregulation leads to oncogenes leads to cancer

Question 26

tumour suppressor genes

Answer 26

anti cell division p16^INK4A p14^ARF p27^KIP1 p21^CIP1 Rb Wee1 deregulation leads to cancer

Question 27

key activators of cell cycle checkpoints

Answer 27

ataxia telangiectasia mutated ATM, double strand break ATM related ATR, single strand break

Question 28

ATR process

Answer 28

phosphorylates CHK1 on serine 345 (p-S345) CHK1 then undergoes auto-phosphorylation on serine 296 (p-S296) CHK1 is an opposing regulator of Wee1 and CDC25A