DNA Repair

Question 1

compare intrastrand vs interstrand covalent cross-linkages

Answer 1

intrastrand- same strand

interstrand- different strand

Question 2

what enzymes are involved in BER?

Answer 2

DNA glycosylases

Question 3

what is the process of BER?

Answer 3

altered base is recognized by DNA glycosylase
glycosylase removes aberrant base 
AP endonucleases remove sugar-phosphate
DNA pol-b fills in gap
DNA ligase rejoins strand

Question 4

what is the process of NER?

Answer 4

damaged DNA recognized
local unwinding of DNA
dual DNA strand excision (2 cuts)
gap filled with DNA pol
nick sealed by DNA ligase

Question 5

what is xeroderma pigmentosa?

Answer 5

high sensitivity to UV light secondary to defect in any 1 of the 7 genes responsible for NER

Question 6

what is an example of a defect fixed by NER?

Answer 6

thymine dimers from UVB exposure

Question 7

what is mismatch repair?

Answer 7

deals with correcting mismatches of the normal bases

Question 8

what are the enzymes used in MMS?

Answer 8

the same enzymes in BER and NER PLUS specialized enzymes- MSHs and MLHs

Question 9

what are MSH enzymes?

Answer 9

mismatch recognition
(at least 5 types in eukaryotes)

Question 10

what are MLH enzymes?

Answer 10

cutting out mismatches

at least 4 types in eukaryotes

Question 11

what mutations can lead to colon CA?

Answer 11

mutations in MLH1 and MLH2 can lead to NHPCC (90%) or 15% of sporadic colon CA

Question 12

how can the MMS differentiate between parent and daughter strand?

Answer 12

parental strand will have more methylation

Question 13

what are 2 examples of physiologic double-strand breaks?

Answer 13

VDJ recombination
class switch breaks

Question 14

what is NHEJ?

Answer 14

non-homologous end jointing; way to fix ds breaks

Question 15

what will necessarily occur with NHEJ?

Answer 15

deletion and mutation

Question 16

what type of cells commonly use NHEJ?

Answer 16

metastatic cancer cells

Question 17

what is homology directed repair?

Answer 17

damage is repaired accurately using information from sister chromatid, RecA mediated

Question 18

what are the enzymes that detect SSB in homology directed repair?

Answer 18

PPAR1/2

Question 19

what are the enzymes that clean out the area in SSB homology directed repair?

Answer 19

TDP1 and PNKP

Question 20

what is the enzyme complex that detects DSB in homology directed repair?

Answer 20

DNA PKcs+Ku70+Ku80

Question 21

what are the enzymes that clean out the area in DSB homology directed repair?

Answer 21

PNKP and artemis

Question 22

what is responsible for 60-80% of inherited breast CA?

Answer 22

mutationsin BRCA1/2

Question 23

what is the action of BRCA1

Answer 23

recruited to sites of DNA damage, regulates homologous recombination and NHEJ

Question 24

what is the action of BRCA2

Answer 24

regulates homologous recombination

Question 25

describe ataxia telangectasia

Answer 25

caused by mutations on the ATM gene that cause it to miss dsDNA breaks, assoc with increased risk breast CA

Question 26

describe fanconi anemia

Answer 26

caused by defects in DNA repair

Question 27

describe bloom syndrome

Answer 27

caused by mutations in DNA helices

Question 28

describe cockayne syndrome

Answer 28

caused by defect in transcription-lined DNA repair

Question 29

describe Werner’s syndrome

Answer 29

caused by mutation in DNA helices gene, results in premature aging