Cell cycle - principle of regulation

Question 1

phase of cell cycle

Answer 1

G1 -> S -> G2 -> M phase (mitosis)

Question 2

cell cycle timing and structure

Answer 2

varies in different cells and organisms

Question 3

mechanism control

Answer 3

similar in all eukaryotes

Question 4

common model system

Answer 4

unicellular yeast
embryo of frogs/ flies
mammalian cells

Question 5

making model for the mechanism of cell cycle

Answer 5

combine data to show principles of regulation are same

Question 6

cycle progression study methods

Answer 6

using flow cytometry - study individual cells
using fluorescence
based on DNA content

Question 7

check point of cell cycle control system

Answer 7

making certain decision on whether to progress

control timing and coordination of cell cycle event

Question 8

system in cell cycle control

Answer 8

robust and reliable biochemical timer but high adaptable - can be modified

Question 9

first stage - start transition

Answer 9

is it environmentally favourable
before S phase
prevent progression if cell growth is insufficient

Question 10

Cell growth being insufficient

Answer 10

DNA damage

Question 11

if DNA damage occurs

Answer 11

cell enter prolonged non-dividing state until conditions are met

Question 12

stage 2 - G1/M transition

Answer 12

all DNA replicated? environment being favourable?

regulatory transition controlled by various factors

Question 13

factors the control regulatory transition

Answer 13

DNA damage or completion of DNA replication

Question 14

stage 3 - metaphase to anaphase transition

Answer 14

all chromosomes attached to spindle

Question 15

initiation of sister chromatid separation could be blocked

Answer 15

if chromosomes are not properly attached to MT of mitotic spindle

Question 16

checkpoints if something goes wrong

Answer 16

arrest cycle at transitions

launch events in complete reversible fashion

Question 17

cell cycle control system depends on

Answer 17

based on cyclically activated Cdk

Question 18

Cdk

Answer 18

cyclin dependent kinase

without cyclin, Cdk is inactive

Question 19

cyclin + Cdk

Answer 19

complex

Question 20

cyclin-Cdk complex

Answer 20

protein kinase is activated to trigger specific cell cycle events

Question 21

different types of cyclins

Answer 21

form different cyclin-Cdk complex which trigger different cycle events

Question 22

G1/S - cyclin

Answer 22

activate at start of G1/S-Cdk - progression through start

Question 23

Concentration of G1/S - cyclin

Answer 23

concentration decreases as S-Cdk activated

Question 24

S - cyclin

Answer 24

activate Cdk for DNA synthesis therefore remains high

Question 25

Concentration of S - cyclin

Answer 25

increases at start and decreases at metaphase-anaphase

Question 26

M-cyclin

Answer 26

activate Cdk for entry into mitosis

Question 27

Concentration of M-cyclin

Answer 27

increases to mitosis and peak in metaphase

Question 28

G1 concentration

Answer 28

increases depending on rate of cell growth of promoting signals

Question 29

G1

Answer 29

activates Cdk stimulating entry of new cell cycle at start

Question 30

function of cyclins

Answer 30

activates Cdks partner and direct it to specific target protein therefore complex phosphorylates different set of substrate proteins

Question 31

some complex function

Answer 31

induce different effect at different times in cycle | as some Cdk substrate accessibility changes during cycle

Question 32

regulating activities of complex

Answer 32

CAK Wee 1 Cdc 25 regulatory pathway Cdk inhibitor protein

Question 33

CAK - Cdk activating kinases

Answer 33

3 states : inactive, partially active, fully active

Question 34

CAK - inactive stage

Answer 34

without cyclin bound | active site blocked by region of protein (T-loop)

Question 35

CAK - partially active

Answer 35

cyclin bind therefore T-loop moves out of active site

Question 36

CAK - fully active

Answer 36

phosphorylation of Cdk 2 at threonine residue in T-loop activate enzyme to change shape of T-loop to improve ability of enzyme to bind to protein substrate

Question 37

Wee 1-Cdc 25 regulatory pathway function

Answer 37

cyclin-cdk complex can be inhibited by phosphorylation at 1/2 sites in active site of enzyme

Question 38

Wee 1-Cdc 25 - inactive

Answer 38

phosphorylation of Tr15 by wee/ both Thr 14 and Tyr by Myt 1

Question 39

Wee 1-Cdc 25 - reactivates

Answer 39

dephosphorylation by phosphatase Cdc 252

Question 40

Cdk inhibitor protein - CKI

Answer 40

bind to complexes therefore inactive complex

Question 41

CKI binding

Answer 41

large rearrangement in structure of Cdk active site = inactive

Question 42

use of CKI binding

Answer 42

govern activities of G1/S and S-Cdks early in cycle

Question 43

CKI

Answer 43

interacts with Cdks or Cdk-cyclin complex blocks activity during G1 or as a response to inhibitory signals from environment/damage DNA

Question 44

How mechanism regulate cell cycle - e.g DNA damage

Answer 44

signalling pathway activated

Question 45

process of mechanism regulating cell cycle

Answer 45

Kinase transmitted to p53 | p53 phosphorylates in response to DNA damage forming stable active p53

Question 46

process of using stable active p53 in regulating DNA damage in cell cycle

Answer 46

binds in nucleus to certain promoter of gene and bind to regulating region such as p21 all transcription of translation of p21

Question 47

p21

Answer 47

Cdk inhibitor protein

Question 48

p53

Answer 48

protein for major cell cycle regulator | transcription regulator

Question 49

what else is involved in regulation of cycle

Answer 49

signal transduction via multi-step signalling pathway

Question 50

regulated proteolysis process of forming polyubiquitin chain

Answer 50

Ub transferred to E1 - activated and then it is transferred to E2 covalently attached to target protein by E3 Ub ligase forming polyubiquitin chain

Question 51

regulated proteolysis process after formation of polyubiquitin chain

Answer 51

26s proteasome recognises polyubiquitylated protein and destroys it

Question 52

Ub

Answer 52

ubiquitin

Question 53

E1

Answer 53

ATP dependent manner

Question 54

process of destroying polyubiquitin chain

Answer 54

ATP dependent

Question 55

E3 Ub ligase has 4 classes

Answer 55

HECT-type RING-finger type PHD-finger type U-box type

Question 56

RING finger type subfamily

Answer 56

cullin based E3s such as SCF - SKP1-CUL1-F-box protein or APC/C - Anaphase-promoting complex/ cyclosome

Question 57

SCF

Answer 57

ubiquitylates substrate - late G1 to early M

Question 58

SCF activators

Answer 58

Skp2 FBW7 beta-TRCP

Question 59

APC/C

Answer 59

active in mid M (anaphase) to late G1

Question 60

APC/C activators

Answer 60

Cdc20 Cdn1

Question 61

control of mitosis by APC/C

Answer 61

regulated proteolysis

Question 62

M-Cdk in controlling mitosis

Answer 62

promotes early mitosis and activation of APC/C(Cdc20) triggering anaphase and mitotic exit - stimulating destruction of regulatory proteins

Question 63

cyclin destruction

Answer 63

Cdk inactivation APC/C(Cdc20) and triggers activation of APC/C(Cdn1) - continued APC/C activity in G1

Question 64

APC activiation

Answer 64

triggers sister-chromatid separation at M to A tranisiton

Question 65

what APC/C does in controlling mitosis

Answer 65

destruction of S and M cyclin therefore inactivation of Cdk | therefore completion of mitosis and cytokinesis