DNA Repair

Question 1

what 3 things do you need for cancer

Answer 1

1. mutation/mismatch in a gene of self proliferation 2. repair mechanisms have to miss it or be too busy to fix it 3. self destructive pathway can’t turn on it has to be mutated

Question 2

2 diseases from mutation in DNA repair pathways

Answer 2

cockaynes syndrome and xeroderma pigmentosum

Question 3

exogenous sources of DNA damage include

Answer 3

UV radiation and chemicals

Question 4

endogenous sources of DNA damage

Answer 4

ROS, alkylation, hydrolysis

Question 5

what repair pathway fixes deprivation or depyrimidination

Answer 5

BER

Question 6

what repair pathway fixes spontaneous deamination (ACG)

Answer 6

BER

Question 7

why are UV induced thimine dimers bad

Answer 7

distort DNA–> Pol III falls off trying to replicate so Pol II takes over–> pol II doesn’t have proofreading so that causes a lot of errors and mismatches and mistakes

Question 8

what pathway fixes UV damage

Answer 8

direct reversal, NER or TLS

Question 9

what fixes base alkylation

Answer 9

direct reversal, BER and MMR

Question 10

what fixes base oxidation by ROS

Answer 10

BER and MMR

Question 11

what fixes uracil in DNA

Answer 11

BER

Question 12

what causes uracil in DNA

Answer 12

deaminatino of a cytosine residue to make uracil in the DNA

Question 13

indels in DNA can be fixed through

Answer 13

NER

Question 14

bulky chemical adducts can be fixed by

Answer 14

NER and TLS

Question 15

replication errors aka mismatch can be fixed by

Answer 15

MMR

Question 16

intra/interstrand corsslinks are repaired by

Answer 16

SSBR and NER

Question 17

DNA strand breaks are fixed by

Answer 17

direct reversal, SSBR and DSBR

Question 18

double stranded breaks are fixed by

Answer 18

homologous recombination and non homologous end joining (the latter is the major form of fixing)

Question 19

what fixes stalled replication forks

Answer 19

DSBR

Question 20

in direct reversal, what enzyme fixes ssDNA breaks

Answer 20

DNA ligase

Question 21

in direct reversal, what enzyme fixes UV caused thymine dimers

Answer 21

photolyase

Question 22

what enzyme in direct reversal fixes base alkylation

Answer 22

methyltransferase MGMT

Question 23

tumors that have associations with MGMT result in what

Answer 23

reduction in the ability of DNA repair

Question 24

what do all excision repair pathways need

Answer 24

1. to recognize the damage and need an endonuclease and/or exonuclease, DNA polymerase, and DNA ligase

Question 25

what does BER require specifically

Answer 25

glycosylases that each recognize a specific type of altered base

Question 26

4 steps of BER

Answer 26

1. glycosylase flips altered base out and then hydrolyzes the N glycosidic bond to remove the damaged base, 2. this is now an AP site that gets removed by an AP specific endonuclease and AP lyase 3. gap filled by DNA polymerase 4. Nick is sealed by DNA ligase

Question 27

2 pathways of NER

Answer 27

1. global genome NER (recognizes distortion anywhere on genome) and 2. transcription coupled NER ( recognizes it in areas that are being actively transcribed)

Question 28

5 steps in NER

Answer 28

1. DNA is recognized by a multi protein complex with endonuclease activity 2. cuts one strand of the phosphodiester backbone on both sides of the DNA to generate an oligonucleotide with the damage nucleotide 3. helices unwinds DNA and releases the ss oligonucleotide that includes the lesion 4. DNA polymerase comes in and inserts nucleotides complimentary to the intact DNA strand 5. DNA ligase seals phosphodiester backbone

Question 29

3 diseases associated with problems with NER

Answer 29

cockayne syndrome, xeroderma pigmentosum, trichothiodystropy

Question 30

two bacterial proteins involved in MMR

Answer 30

mutS and mutL

Question 31

mammalian homologs to MutS and MutL

Answer 31

MSH and MLH

Question 32

how does MMR recognize the new DNA strand in proks

Answer 32

it isn’t yet methylated

Question 33

whats the problem with lesion bypass or translesion synthesis

Answer 33

highly mutagenic because it uses DNA pol II that can’t proofread