White: Cell cycle 1&2

Question 1

Chromosomal duplication and segregation occur in which phase(s) of the cell cycle

Answer 1

Duplication- S phase

Segregation- M phase

Question 2

G1 phase occurs between

Answer 2

M and S

Question 3

G2 phase occurs between

Answer 3

S and M

Question 4

Checkpoint I

Answer 4

START- cell commits to cell cycle entry and chromosome duplication

Question 5

Checkpoint II

Answer 5

G2/M- Chromosome alignment on spindle in metaphase

Question 6

Checkpoint III

Answer 6

Metaphase-to-anaphase - Trigger sister chromatid separation and cytokinesis

Question 7

Cdk function

Answer 7

Phosphorylate proteins downstream to activate them and regulate cell cycle events
The cell cycle is governed by Cdks

Question 8

Cyclins function

Answer 8

Proteins that regulate Cdks
Cdks must be bound to cyclin to be active and have protein kinase activity
Direct Cdks to their specific target

Question 9

What is the variation in cyclin and Cdk levels throughout the cycle, if any?

Answer 9

Cyclin levels vary according to point of time in cell cycle, Cdk levels are constant

Question 10

G1/S cyclins function

Answer 10

Start cell cycle
Activate Cdks in late G1
Help trigger progression through start
Commitment made to cell cycle entry
Levels drop in S phase

Question 11

S cyclins functions

Answer 11

Bind Cdks after progression through start
Help stimulate chromosome duplication
S-cyclin levels remain high until mitosis

Question 12

M cyclins functions

Answer 12

Activate Cdks that stimulate entry into mitosis at G2/M checkpoint
Removed at about the middle of mitosis

Question 13

CAK function

Answer 13

Cdk activating kinase

Phosphorylates Cdks to activate them

Question 14

Wee1 Kinase

Answer 14

Inhibits Cdk activity by phosphorylating the “roof site” on Cdks

Question 15

Cdc25

Answer 15

Phosphotase that dephosphorylates “roof site” to increase Cdk activity

Question 16

CKI proteins

Answer 16

Cdk inhibitory proteins

Binds to both Cdk and cyclin to inactivate

Question 17

SCF-ubiquitin ligase

Answer 17

Adds ubiquitin to CKIs to target for destruction

This activates the S-Cdks

Question 18

SCF activity depends on

Answer 18

F-box subunit

Question 19

M-Cdk is activated how

Answer 19

Cdc25 protein phosphatase removes inhibitory phosphates from M-Cdk

Question 20

Progression from metaphase to anaphase is triggered by

Answer 20

Protein destruction, NOT PROTEIN PHOSPHORYLATION

Question 21

APC/C

Answer 21

Anaphase-promoting complex
Catalyzes addition of ubiquitin to protein securin (which inhibits separase from cleaving cohesin)
Causes ubiquination of M-cyclins and S-cyclins
Activated by binding to Cdc20

Question 22

Cohesin

Answer 22

Glues together sister chromatids along their length

Question 23

Securin

Answer 23

Protects cohesin protein linkages that hold sister chromatid pairs together by inhibiting separase (an enzyme that cleaves cohesin)

Question 24

PRE-RCs

Answer 24

Pre-replicative complexes
Assembly of PRE-RC is inhibited by Cdk activity
While S-Cdk and M-Cdk levels are high during S and M stage, NO PRE-RC is formed

Question 25

Condensin

Answer 25

At the end of S phase, forms ring-like structures and uses ATP to promote compaction and resolution of sister chromatids (untangle them so they can be separated)

Question 26

What triggers prophase, anaphase, prometaphase and metaphase

Answer 26

Increase of M-Cdk activity at G2/M

Question 27

Kinetochore microtubules

Answer 27

Attach each chromosome to spindle pole

Question 28

Interpolar microtubules

Answer 28

Hold two halves of spindle together

Question 29

Astral microtubules

Answer 29

Interact with cell cortex

Question 30

Dyneins

Answer 30

Minus-end directed motors Link plus ends of astral microtubules to actin filaments at cell cortex -By moving towards minus end of microtubule, the dynein motors pull the spindle poles away from eachother

Question 31

Kinesin-5

Answer 31

Two motor domains that interact with plus ends of anti-parallel microtubules Moves these two anti-parallel microtubules past each other to force the spindle poles apart If there is no Kinesin-5, the spindle collapses

Question 32

Kinesin-14

Answer 32

Minus-end directed motor, pulls poles together

Question 33

Kinesin-4,10

Answer 33

Chromokinesins- plus-end directed motors | Push attached chromosomes away from the pole

Question 34

Kinetochore

Answer 34

Responsible for attachment of spindle to chromosomes There is an exposed open end for addition and removal of tubulin subunits from microtubules attached to kinetochore Removal of tubulin subunits leads to force pulling kinetochore/chromosomes to pole of cell

Question 35

3 Forces in chromosome movement

Answer 35

Depolymerization Microtubule flux Polar ejection force

Question 36

Depolymerization

Answer 36

Depolymerization of the plus end of the microtubule drives the pulling of the kinetochore towards the pole

Question 37

Microtubule flux

Answer 37

Tubulin added at plus end while being removed at minus end | -Occurs on interpolar microtubules

Question 38

Polar ejection force

Answer 38

Kinesin-4,10 motors on chromosomes interact with microtubules and transport chromosomes from poles Results in push-pull phenomenon

Question 39

Anaphase A

Answer 39

Chromosomes move apart | -Due to spindle microtubule depolymerization at kinetochore

Question 40

Anaphase B

Answer 40

Separation of spindle poles themselves | -By kinesin-5 motor proteins (also dynein pulls pole apart)

Question 41

Mitogens

Answer 41

Stimulate cell division by triggering G1/S-Cdk activity

Question 42

Survival factos

Answer 42

Suppress form of programmed cell dealth (apoptosis)

Question 43

Mitogen Cell-cycle entry into S-phase

Answer 43

Mitogen binds receptor Ras causes activation of MAP kinase cascade Increase of gene regulatory proteins including Myc Myc promotes entry into cell cycle by increasing expression of G1 cyclins G1-Cdk-Cyclin activates gene regulatory factors called E2F proteins E2F binds promotors of G1/S cyclin and S cyclin genes (leads to DNA transcription)

Question 44

Rb protein

Answer 44

Tumor supressor protein E2F protein is inhibited by interacting with Rb protein Shuts down entry into S-phase Active G1-Cdk phosphorylates Rb to reduce binding to E2F

Question 45

What happens if Rb protein is inactive

Answer 45

No control going into cell cycle so cancer can occur (retinoblastoma)

Question 46

ATM and ATR protein kinases

Answer 46

Activated by DNA damage | Phosphorylate Chk1 and Chk2 proteins

Question 47

Chk1/2 proteins

Answer 47

Major target is p53 protein, which stimulates transcription of p21

Question 48

p21 CKI

Answer 48

Binds to G1/S-Cdk and S-Cdk to inhibit activity (no cell division- damaged DNA must be repaired)

Question 49

What if ATM/ATR proteins are not working

Answer 49

This can cause Ataxia telangiectasia and other cancers

Question 50

Ras is mutated in __% of cancers, p53 is mutated in __% of cancers

Answer 50

Ras mutated in 30% of cancers | p53 mutated in 50% of cancers

Question 51

PI-3 kinase pathway

Answer 51

Most important growth signaling pathway PI-3 kinase adds ATP to inositol phospholipids Activates TOR, which activates many factors for cell growth