genome instability and mutation part 2

Question 1

what molecules detect damage to DNA

Answer 1

ATM/ATR

Question 2

what do ATM/ATR activate

Answer 2

downstream molecules such as P53, Chk1, Chk2

Question 3

what are single nucleotide varients

Answer 3

substitution of one base at a nucleotide

Question 4

what is insertion or deletion

Answer 4

gain/loss of one or hundreds of nucleotides

Question 5

what are translocations

Answer 5

rearrangement of non homologous chromosomes

Question 6

what is aneuploidy

Answer 6

gain or loss of entire chromosomes

Question 7

what is microsatellite instability

Answer 7

variation in short repeats found in the genome

Question 8

mutations: common single nucleotide varient

Answer 8

P53 point mutations

Question 9

mutations: insertions and deletions in cancer

Answer 9

many oncogenes are mutated or amplified and TSGs are deleted or inactivated

Question 10

mutations: inversions

Answer 10

section of DNA flips itself around

Question 11

mutations: aneuploidy

Answer 11

if the mitotic checkpoint isn’t working then there is not proper chromosome segreation

Question 12

mutations: microsatellite instability

Answer 12

highly variable from person to person, set length in individuals so can be genetic fingerprint, the sequences become unstable and can shorten or lengthen

Question 13

when does microsatellite instability occur

Answer 13

when there is a defect in mismatch repair

Question 14

why are mutations important?

Answer 14

when they can confer a selective advantage to cells e.g. increase proliferation and decrease apoptosis often have a selective advantage and result in clonal cancer

Question 15

mutations and cancer

Answer 15

they drive cancer and make it become more aggressive overtime and resistant to treatment

Question 16

which genes are commonly mutated in cancer

Answer 16

P53 and other TSGs are inactivated, RAS and EGFR are mutated oncogenes

Question 17

what happens if theres a mutation in a damage and response gene (‘caretaker genes’)?

Answer 17

less protective mechanisms in the cell so it becomes more prone to further mutation etc…

Question 18

tumour heterogeneity

Answer 18

different genotypes and phenotypes within a cancer due to different mutations within different cells. Different mutations are selected for.

Question 19

UV light and skin cancer

Answer 19

UV light is absorbed by pyrimidine bases which makes them reactive and if its next to another pyrimidine it can form pyrimidine dimers e.g. c-c

Question 20

smoking and lung cancer

Answer 20

smoking causes bulky and oxidative (small adducts) damage. risk of P53 mutations strongly associated with heavy tobacco consumption. Polycyclic aromatic hydrocarbons in the smoke causes mutations at sites susceptible to adducts

Question 21

infections and cancer

Answer 21

infections are associated with inflammation (increase ROS) and can induce DNA damage

Question 22

what cancer stems from hepatitis B/C

Answer 22

liver

Question 23

what cancer is associated with helicobacter pylori

Answer 23

stomach

Question 24

functional redundancy in DNA repair pathways

Answer 24

when one pathway does not work, the cell can alter DNA so that another pathway repairs the DNA

Question 25

what happens when DNA damage response pathways fail

Answer 25

only somatic mutations tend to occur and they result in mutator phenotype and cancer

Question 26

what repair pathway is used for hereditary nonpolyposis colorectal cancer and what mutations occur

Answer 26

MMR, mutations in MutS/MutL which can be detected by MSI

Question 27

what repair pathway is used for hereditary breast and ovarian cancer and what mutations occur

Answer 27

DSBR, BRCA1/2 genes are mutated which are important in homologous recombination pathway

Question 28

what repair pathway is used for xeroderma pigmentosum and what mutations occur

Answer 28

NER, bulky adducts result in slow neurodegeneration

Question 29

what repair pathway is used for cockayne syndrome and what symptoms

Answer 29

NER, sensitivity to sunlight and growth retardation

Question 30

what repair pathway is used for Li Fraumeni and what mutations occur

Answer 30

DNA damage sensing, P53 mutation

Question 31

what repair pathway is used for Ataxia telangiectasia and what mutations occur

Answer 31

DNA damage sensing, ATM mutation