3- instability and repair

Question 1

genomic instability

Answer 1

accumulation of unintended alterations to genomic sequences

Question 2

genomic instability refers to an elevated _____

Answer 2

mutation rate

Question 3

major forms of genomic instability

Answer 3

1. gross chromosomal abnormalities
2. subtle sequence changes (nucleotide instability)

Question 4

what are examples of gross chromosomal abnormalities

Answer 4

1. ploidy alterations
2. gene amplification
3. chromosomal structural alterations

Question 5

examples of subtle sequence changes

Answer 5

1.point mutations
2. microsatellite instability

Question 6

how do chromosomal abnormalities and mutations arise? AKA genomic instability causes

Answer 6

1. spontaneous events
2. intrinsic stresses
3. extrinsic stresses

Question 7

what are some consequences to damaging dna

Answer 7

1. cell cycle arrest
2. apoptosis
3. cancer
4. aging
5. inborn disease

Question 8

what the dna repair mechanisms

Answer 8

1. double stranded dna break repair
2. nucleotide excision repair
3. base excision repair
4. mismatch repair
5. cell cycle checkpoints

Question 9

DSB is produced by

Answer 9

free radicals , various chemicals, replication across single stranded DNA breaks

Question 10

what are the 2 mechanisms for DSB repair

Answer 10

non homologous end joining
homologous recombination

Question 11

characteristics about non homologous end joining

Answer 11

-potentially error prone
-critical for immunoglobulin gene rearrangement
-limited links to cancer

Question 12

characteristics about homologous recombination

Answer 12

-precise
-highly conserved
-core factors: essential
-accessory factors: linked to disease

Question 13

how does excision repair work

Answer 13

1. recognition of damage
2. removal of ssDNA containing lesion
3. repair replication across gap
4. ligation of the repaired strand

Question 14

what are the lesions of nucleotide excision repair

Answer 14

bulky, helix distorting damage

Question 15

what are the lesions of base excision repair

Answer 15

small base alterations

Question 16

mech of base excision repair

Answer 16

-damaged base is flipped out of helix and cleaved
-recognized by endonuclease that cleaves the backbone
-polymerases can repair the site

Question 17

lesions of mismatch repair

Answer 17

mismatches, insertion/deletion loops

Question 18

mech of mismatch repair

Answer 18

lesions are identified by complexes and then additional factors are recruited to the damage site. the defective sequence is excised and DNA is resynthesized using the intact strand

Question 19

cell cycle checkpoints=

Answer 19

dna damage checkpoints

Question 20

cell cycle checkpoints function

Answer 20

1. sense and respond to the presence of DNA damage by arresting cell cycle progression
2. monitor and ensure completion of major cell cycle events

Question 21

the mitotic spindle checkpoint ensures that

Answer 21

chromosomes are properly aligned on the metaphase spindle before chromosome segregation

Question 22

DNA damage checkpoints respond to

Answer 22

genome damage by arresting cell cycle progression and promoting DNA repair

Question 23

dna damage signal cascade

Answer 23

signal–> sensor –> transducers –> effectors –> cell cycle arrest/DNA repair/replication fork stabilization

Question 24

cancer cells appear to be highly dependent on

Answer 24

stress response mechanisms

Question 25

activated oncogenes stimulate ____ leading to DNA damage

Answer 25

hyperproliferation

Question 26

cancer cells are susceptible to certain drugs that target

Answer 26

stress response pathway

Question 27

senescence

Answer 27

DNA damage response to shorted telomeres

Question 28

what is Ames test

Answer 28

a test to determine the mutagenic activity of chemicals by observing whether they cause mutations in sample bacteria
-tests carcinogenicity

Question 29

what type of mutations are oncogenes

Answer 29

homozygous dominant or recessive

Question 30

how do cancer cells achieve immortality

Answer 30

cancer cells keep high levels of telomerase, an enzyme that prevents telomerase shortening
-this gives the ability of the chromosomes to continue to replicate forever