Cell cycle - principle of regulation Flashcards

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1
Q

phase of cell cycle

A

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

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2
Q

cell cycle timing and structure

A

varies in different cells and organisms

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3
Q

mechanism control

A

similar in all eukaryotes

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4
Q

common model system

A

unicellular yeast
embryo of frogs/ flies
mammalian cells

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5
Q

making model for the mechanism of cell cycle

A

combine data to show principles of regulation are same

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6
Q

cycle progression study methods

A

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

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7
Q

check point of cell cycle control system

A

making certain decision on whether to progress

control timing and coordination of cell cycle event

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8
Q

system in cell cycle control

A

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

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9
Q

first stage - start transition

A

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

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10
Q

Cell growth being insufficient

A

DNA damage

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11
Q

if DNA damage occurs

A

cell enter prolonged non-dividing state until conditions are met

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12
Q

stage 2 - G1/M transition

A

all DNA replicated? environment being favourable?

regulatory transition controlled by various factors

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13
Q

factors the control regulatory transition

A

DNA damage or completion of DNA replication

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14
Q

stage 3 - metaphase to anaphase transition

A

all chromosomes attached to spindle

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15
Q

initiation of sister chromatid separation could be blocked

A

if chromosomes are not properly attached to MT of mitotic spindle

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16
Q

checkpoints if something goes wrong

A

arrest cycle at transitions

launch events in complete reversible fashion

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17
Q

cell cycle control system depends on

A

based on cyclically activated Cdk

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18
Q

Cdk

A

cyclin dependent kinase

without cyclin, Cdk is inactive

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19
Q

cyclin + Cdk

A

complex

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20
Q

cyclin-Cdk complex

A

protein kinase is activated to trigger specific cell cycle events

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21
Q

different types of cyclins

A

form different cyclin-Cdk complex which trigger different cycle events

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22
Q

G1/S - cyclin

A

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

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23
Q

Concentration of G1/S - cyclin

A

concentration decreases as S-Cdk activated

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24
Q

S - cyclin

A

activate Cdk for DNA synthesis therefore remains high

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25
Q

Concentration of S - cyclin

A

increases at start and decreases at metaphase-anaphase

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26
Q

M-cyclin

A

activate Cdk for entry into mitosis

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27
Q

Concentration of M-cyclin

A

increases to mitosis and peak in metaphase

28
Q

G1 concentration

A

increases depending on rate of cell growth of promoting signals

29
Q

G1

A

activates Cdk stimulating entry of new cell cycle at start

30
Q

function of cyclins

A

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

31
Q

some complex function

A

induce different effect at different times in cycle

as some Cdk substrate accessibility changes during cycle

32
Q

regulating activities of complex

A

CAK
Wee 1 Cdc 25 regulatory pathway
Cdk inhibitor protein

33
Q

CAK - Cdk activating kinases

A

3 states : inactive, partially active, fully active

34
Q

CAK - inactive stage

A

without cyclin bound

active site blocked by region of protein (T-loop)

35
Q

CAK - partially active

A

cyclin bind therefore T-loop moves out of active site

36
Q

CAK - fully active

A

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

37
Q

Wee 1-Cdc 25 regulatory pathway function

A

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

38
Q

Wee 1-Cdc 25 - inactive

A

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

39
Q

Wee 1-Cdc 25 - reactivates

A

dephosphorylation by phosphatase Cdc 252

40
Q

Cdk inhibitor protein - CKI

A

bind to complexes therefore inactive complex

41
Q

CKI binding

A

large rearrangement in structure of Cdk active site = inactive

42
Q

use of CKI binding

A

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

43
Q

CKI

A

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

44
Q

How mechanism regulate cell cycle - e.g DNA damage

A

signalling pathway activated

45
Q

process of mechanism regulating cell cycle

A

Kinase transmitted to p53

p53 phosphorylates in response to DNA damage forming stable active p53

46
Q

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

A

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

47
Q

p21

A

Cdk inhibitor protein

48
Q

p53

A

protein for major cell cycle regulator

transcription regulator

49
Q

what else is involved in regulation of cycle

A

signal transduction via multi-step signalling pathway

50
Q

regulated proteolysis process of forming polyubiquitin chain

A

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

51
Q

regulated proteolysis process after formation of polyubiquitin chain

A

26s proteasome recognises polyubiquitylated protein and destroys it

52
Q

Ub

A

ubiquitin

53
Q

E1

A

ATP dependent manner

54
Q

process of destroying polyubiquitin chain

A

ATP dependent

55
Q

E3 Ub ligase has 4 classes

A

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

56
Q

RING finger type subfamily

A

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

57
Q

SCF

A

ubiquitylates substrate - late G1 to early M

58
Q

SCF activators

A

Skp2
FBW7
beta-TRCP

59
Q

APC/C

A

active in mid M (anaphase) to late G1

60
Q

APC/C activators

A

Cdc20 Cdn1

61
Q

control of mitosis by APC/C

A

regulated proteolysis

62
Q

M-Cdk in controlling mitosis

A

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

63
Q

cyclin destruction

A

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

64
Q

APC activiation

A

triggers sister-chromatid separation at M to A tranisiton

65
Q

what APC/C does in controlling mitosis

A

destruction of S and M cyclin therefore inactivation of Cdk

therefore completion of mitosis and cytokinesis