Cell Cycle pt. 1

Question 1

M phase

Answer 1

mitosis

Question 2

G0 phase

Answer 2

quiescent, intact proliferation capacity, non-cycling

Question 3

G1 phase

Answer 3

duration between completion of cell division and intitiation of DNA replication where cells start building mass

Question 4

S phase:

Answer 4

DNA replication

Question 5

G2 phase

Answer 5

duration between completion of DNA replication and initiation of cell division

Question 6

positive regulators of cell cycle

Answer 6

cyclins and CDKs

Question 7

negative regulators of cell cycle

Answer 7

cyclin dependent kinase inhibitors (CKIs)

Question 8

Cyclin B is in

Answer 8

made in G2
peaks in M
stops at end of M

Question 9

Nuclear D1 is in

Answer 9

made in G1
peaks in G1
stops in S

Question 10

cyclin E is in

Answer 10

made in g1
peaks at Rpoint
stops in S

Question 11

cyclin A is in

Answer 11

made in S
peaks in S
stops in G2

Question 12

cyclins need CDKs because

Answer 12

the CDKs come in and phosphorylate the cyclins to activate them via the T loop. Need 3 P to be active

there needs to be a P on the first site and two other Ps removed from those sites by a protein dephosphatase, example is Cdc25

Question 13

Kinase: Cdk1 (p34) goes with cyclin

Answer 13

A, B1-B2,

Question 14

kinase: Cdk2 goes with cyclin

Answer 14

A, E

Question 15

kinase: Cdk4, Cdk6 goes with cyclin

Answer 15

D1-D3

Question 16

Function of cdk1-A, cdk1-B

Answer 16

triggers G2-M transition

cyclin A is made in S and destroyed in prometaphase.

cyclin B is made in S/G2 and destroyed following the completion of chromsoomes attachement to the spindle

Question 17

function of Cdk2-A, E

Answer 17

triggers G1-S transition

Question 18

function of Cdk4-D, Cdk6-D

Answer 18

P Rb protein in G1

triggers passage of the restriction point and cyclin E synthesis in some cell types

ExC gorwith factors control synthesis of D cyclins

Question 19

Cdc25A phosphatase

Answer 19

substrate: Cdk1, Cdk2
functions: promotes G1 to S transition and G2 to M transition

Question 20

Cdc25B phosphatase

Answer 20

substrate: cdk1
functions: promotes G2 to M transition

Question 21

Cdc25C phosphatase

Answer 21

substrate: cdk1
functions: promotes G2 ro M transition, dephosphosphorylates cdk1 complexed to cyclins A and B

Question 22

CKIs block the action of

Answer 22

CDKs

ensure tight control of the cell cycle/keep balance of division

activated upon cell cycle checkpoint activation

inactivate by inhibitor binding and phosphorylation interference

Question 23

Two main types of CKI

Answer 23

Ink (p16, 15, 18, 19) family acting on D-CDK4/6

p57, 27, 21 family acting on the E-CDK2, A-CDK2, A-CDC2, B-CDC2

Question 24

When INK4 binds to the cdk,

Answer 24

it twists the cdk upper lobe and blocks the cyclin binding or interferes with ATP hydrolysis

Question 25

when p27 or 21 binds,

Answer 25

a loop binds to the upper lobe of the Cdk and blocks ATP binding (interferes with ATP, ATP can’t bind)

Question 26

CKI: p21

Answer 26

substrate: most cdk-cyclin complexes
function: induced by p53, causes cell cycle arrest after DNA damage

binds PCNA and inhibits DNA synthesis.

promotes cell senescence and terminal differentiation

Question 27

CKI: p27

Answer 27

substrate: most cdk-cyclin complexes
functions: cell cycle arrest in response to growth suppresors like TGF-B and in contact inhibition and differentiation

Question 28

INK4: p16

Answer 28

substrate: cdk4, cdk6
functions: cooperates with Rb protein in growth regulation

cell-cycle arrest in sensence

altered in many cancers

overlaps with p19 an important regulator of p53 tumor supressor protein

Question 29

Ras Superfamily

Answer 29

small GTPases activated by mitogen binding to receptor

turns on MAP kinase which makes the Myc gene

Myc gene makes Myc which is a transcription factor

Myc transcribes a bunch of proteins for cell cycle control

Question 30

Myc effects

Answer 30

increased cyclin D, increased p27 degradation, increased E2F synthesis, Rb phosphorylation, and entry into S phase

Question 31

Restriction point

Answer 31

between G1/S transition

unphosphorylated pRb gets P by D-CDK4

in its hypophosphorylated phase, it hits the restriction point

once it is hyperphosphorylated, it is comited to continuing through the cell cycle

this is a positive feedback loop

Question 32

during the S phase know that

Answer 32

CDK/cyclin A is stabilizing the prereplciation complex

Question 33

G2/M phase transition

Answer 33

cdk1 is inactive, cyclin B1 is around but not bound

cdk1 dephosphorylation kicks off the two Psand makes Cdk1 active and it binds to cyclin B1

once it forms it can go to mitosis (M phase) and be used then gets ubiquinated for degradation and inactive Cdk1 is back in g1

Question 34

G1 checkpoint pathway (after DNA damage-cell needs to not replicate): slow pathway

Answer 34

ATM makes Mdm wtih p53

p53 makes p21

p21 inhibits cell cycle, stuck in G1

Question 35

G1 checkpoint pathway (after DNA damage): fast pathway

Answer 35

ATM makes Chk2 which interrupts/breaks Cdc25 which inhibits cell cycle, stuck in G1

Question 36

p53 is mutated in

Answer 36

almost every cancer

Question 37

Cells stuck in the G1 checkpoint can

Answer 37

eventually go back into the cell cycle if they are repaired

Question 38

ARP/p16 pathway (G1 checkpoint)

Answer 38

downstream signaling, G1 arrests via p53 and p21 or directly CDK1 p16 will prevent Rb Phosphoryaltion via inhibition of the CDK4 and CDK6 kinases

responds to dna damage and other types of damage

cells will almost never go back into cell cycle from here

Question 39

G2 checkpoint: ATM

Answer 39

ATM makes mdm2 with p53
p53 makes p21
p21 makes cyclinB-cdk1 (phosp)
cyclin B-cdk1 is dephospho. by Cdc25 and then inhibits further progression into the cell cycle

Question 40

G2 checkpoint: ATR

Answer 40

ATR makes chk1 and chk2 which are phosph.
cdc25 comes in a takes off the p
cyclinB-cdk1 come into play from the other pathway and the cell cycle is stopped