L8 - genome instability

Question 1

What is a mutator phenotype?

Answer 1

Gross chr. instability and increased mutation. Often acquired during progression from normal to neoplasia

Question 2

What are cell cycle checkpoints?

Answer 2

Extrinsic control pathways that;

i. Ensure dependency events within cell cycle
ii. ensure viability when cells experience genomic stress

Question 3

What is genetic instabilty?

Answer 3

an elevated rate of genetic mutations

Question 4

What are driver mutations?

Answer 4

Mutations that happen early on and are found in all cancer cells of specific cell type

Question 5

What is the difference between CIN and MIN?

Answer 5

CIN - chr. instability. Gross changes in chr. architecture e.g. aneuploidy/polyploidy
MIN - microsatellite instability. Basically point mutations

Question 6

Does the cell cycle depend on cells undergoing S phase to enter M phase?

Answer 6

No. There are extrinisic controls of the cell cycle. Synthetic lethality screens in yeast identified this

Question 7

What substance was identified to force cells to undergo mitosis when S phase had not been completed?

Answer 7

Caffeine. It was found that caffeine inhibits ATM/ATR which usually act to block mitosis

Question 8

What are the cellular defences to common mutations?

Answer 8

Drugs/ionising radiation - NER, BER and DSB repair
Endogenous DNA damage - BER and direct reversal
DNA rep and processing errors - precursor control, proofreading, mismatch repair

Question 9

What do mutations in cellular defences do?

Answer 9

Push cells toward a mutator phenotpye

Question 10

What is replication stress sensed by?

Answer 10

The presence of ssDNA

Question 11

What is the sensor complex and what does it do?

Answer 11

Sensor complex is a group of proteins that assemble in response to replication stress. It activates Chk1 when blocks anymore DNA replication and recruits repair proteins to the fork for DNA repair