Lecture 23 Cell Cycle II

Question 1

What is condensin?

Answer 1

Five subunit protein complexRelated to cohesinContains 2 SMC subunits and 3 non-SMC subunitsForms ring-like structure and uses ATP to promote compaction and resolution of sister chromatids

Question 2

What triggers assembly of mitotic spindle?

Answer 2

M-Cdk

Question 3

What are kinetochore microtubules?

Answer 3

Attach each chromosome to spindle pole Plus end of each microtubule is attached to sister chromatid pairs at large protein structures called kinetochores

Question 4

What are interpolar microtubules?

Answer 4

Hold two halves of spindle together Plus ends from one pole interact with plus ends from other poles Gamma-turc binds to negative end to nucleate and elongate microtubules

Question 5

What are astral microtubules?

Answer 5

Interact with cell cortex Radiate outward from the poles and contact the cell cortex helping to position the spindle in the cell

Question 6

Describe centrioles

Answer 6

Protein organelles called centrosomes consists of pericentriolar matrix and a pair of centriolesContains gamma-turc > 50 copies

Question 7

Kinesin 5:

Answer 7

two motor domains that interact with plus end of antiparallel microtubule Move the 2 anti-parallel microtubules past each other to force or push the spindle poles apartWalks towards plus end-forces centrosomes apart

Question 8

Kinesin 14:

Answer 8

minus oriented directed motor with a single motor domain Walks towards minus end and pulls poles together

Question 9

How does Kinesin 5 and 14 work together?

Answer 9

5 is pushing poles apart while 14 is pulling the poles together. Why?rope is stretched apart by the push-pull phenomenon. maintain integrity of spindle

Question 10

Kinesin -4,10

Answer 10

Also called chromokinesins Plus directed motorsTowards plus endPush attached chromosomes away from the pole

Question 11

What is the push-pull concept on chromosomes?

Answer 11

Kinetochore microtubule attached to kinetochore causing the chromosome to be pulled towards pole but kinesin 4,10 is pushing chromosome away from pole

Question 12

What are dyneins?

Answer 12

Minus end direct motorsLink plus ends of astral microtubules to actin skeleton at cell cortexBy moving towards minus end of microtubule, the dynein motors pull the spindle poles away from each other

Question 13

What is the outer collar of a kinetochore?

Answer 13

It is the part of the kinetochore that multiple microtubules are attached to There is an exposed open end for addition and removal of tubulin subunits*at first, kinetochore binds laterally to a microtubule and it then slides along chromosome.. Lateral attachment converted to end-on attachment

Question 14

Bi-orientation:

Answer 14

Sister chromatids must attach to opposite poles of mitotic spindle. There for a bipolar attachment is formed from attaching kinetochore to microtubules on opposite side of chromosomeThis is called bi-orientation

Question 15

Depolymerization:

Answer 15

Chromosome movement happens because of 3 forces, one of them being depolymerization.It is a major force that pulls the kinetochore and chromosome towards the spindle pole. By depolymerizing the plus end of the microtubule, it drives the pulling of the kinetochore poleward Pulls collar which is connected to chromosome

Question 16

Microtubule flux:

Answer 16

Chromosome movement is done by 3 forces, microtubule flux is one of them.Microtubules move toward spindle poles while being dismantled at minus ends Tubulin added to plus end while being removed at minus end-interpolar microtubules causing treadmill or escalator

Question 17

What is polar ejection force?

Answer 17

third force that moves chromosomesKinesin-4,10 motors on chromosomes interact with microtubules and transport chromosomes from poles Results in push-pull phenomenon

Question 18

What activates APC/C?

Answer 18

M-Cdk activates APC/C and allows Cdc20 to attached to APC/C to become fully activated

Question 19

What is the difference between Anaphase A and B?

Answer 19

A: chromosomes move apart due to spindle microtubule depolymerization at kinetochoreB: Separation of spindle poles themselves by kinesin-5 motor proteins; also dynein pulls pole apart

Question 20

What is the first visible change in cell during cytokinesis?

Answer 20

Cleavage furrowUnderlying the cleavage furrow is the contractile ringComposed of actin and myosin filaments Rings contract, vesicles fuse with membrane to create new membrane

Question 21

The assembly of ring also results from local formation of new actin filaments which depends on what?

Answer 21

formin : remember, formin is a protein that nucleates assembly of linear, unbranched actin filaments

Question 22

How do mitogens cause cell-cycle entry into S-phase?

Answer 22

mitogens bind to receptorRas causes activation of MAP kinase cascade Leads to increase of gene reg proteins including MycMyc increases expression of G1 cyclinsG1 cyclins activate CdkG1-Cdk activates group of gene reg factors called E2F proteinsE2F binds to promoters of G1/S cycling and S cyclin and DNA synthesis protein genesThen enters into S phase of cell cycle

Question 23

How is E2F protein inhibited?

Answer 23

Rb protein interaction-shuts down entry into S phase

Question 24

What causes E2F to be activated?

Answer 24

Active G1-Cdk phosphorylates Rb to inactivate the Rb protein (reduces binding to E2F)

Question 25

What if Rb protein is not working?

Answer 25

There is no control in going into cell cycle and so cancer can occur = retinoblastoma

Question 26

Retinoblastoma

Answer 26

RareOccurs before age 2Rb is a tumor suppressor and prevents over-roliferation of cellsLoss copies of both Rb genes leads to cell and turmore proliferation of retina

Question 27

How does ATM prevent cancer?

Answer 27

If there is DNA damage due to x-rays for example, the damaged DNA activates ATM and ATR protein kinasesThese kinases associate with site of damage and phosphorylate Chk1 and Chk2 proteinsMajor target of these proteins is p53. p53 upregulates p21 (a CKI)CKI binds to G1/S and S-Cdk to inhibit activity and thus no cell division can occur and DNA can be repaired

Question 28

Ataxia telangectasia

Answer 28

ATM is named from this diseaseRadiation-sensitiveCancer-proneAt patients exhibit higher incidence of lymphoma and leukemiaPoor coordination-clumsy Small dilated blood vessels ATM protein defective Autosomal recessive

Question 29

If cell damage due to xrays is really bad, what occurs?

Answer 29

p53 causes apoptosis of cell

Question 30

What are identified as cancer-promoting genes or oncogenes?

Answer 30

Mitogen activating genesRas mutated in 30% of cancersp53 mutations occur in 50% of human cancers

Question 31

What is the most important growth signaling pathway?

Answer 31

PI-3 kinase pathway PI-3 kinase adds ATP to inositol phospholipids (PIP2)Activates TOR which activates many factors for cell growth

Question 32

What is myostatin?

Answer 32

factors that inhibits muscle cell growthMyostatin inhibitors are being used to treat DMD