Week 1 DNA repair pathways

Question 1

What are the three single nucleotide damage repair pathways?

Answer 1

Mismatch repair, base excision repair, nucleotide excision repair

Question 2

What are the three double strand DNA break repair pathways?

Answer 2

Homologous recombination, non-homologous end joining, and interstrand crosslink repair

Question 3

What is the mechanism of mismatch repair?

Answer 3

Mismatch proofreading proteins scan newly replicated DNA, detects nick in new strand, removes section of replicated daughter strand, repair DNA synthesis

Question 4

Lynch syndrome is a disorder of what DNA repair pathway?

Answer 4

Mismatch repair

Question 5

What types of errors does base excision repair correct?

Answer 5

Small lesions

Question 6

What types of errors does nucleotide excision repair correct?

Answer 6

Large, helix distorting regions

Question 7

What is the mechanism of base excision repair?

Answer 7

DNA glycolase removes altered base pair, AP endonuclease (5’) and lyase (3’) are recruited and remove 1-4ish nucleotides, DNA polymerasefills the gab, DNA ligase seals the gap

Question 8

Xeroderma pigmentosum is a disorder of what DNA repair pathway?

Answer 8

Base excision repair

Question 9

What are the clinical manifestations of Lynch syndrome?

Answer 9

Hereditary colon cancer

Question 10

What are the clinical manifestations of xeroderma pigmentosum?

Answer 10

1000-fold increase of squamous/basal cell carcinomas

Question 11

What is the mechanism of xeroderma pigmentosum?

Answer 11

Mutation in any one of 8 XP genes causes a dysfunctional nucleotide-excision DNA repair complex, which prevents repair of pyrimidine dimers that are formed as a result of ultraviolet light exposure.

Question 12

What is the mechanism of homologous recombination?

Answer 12

ATM recognizes dsDNA breaks, recruits repair proteins (including BRCA1/2), crossing over/strand inversion occurs, DNA is re-synthesized creating two copies of corrected sequence

Question 13

What is the mechanism of non-homologous end joining?

Answer 13

Ku heterodimers recognize dsDNA breaks, recruit DNA protein kinase to align breaks, limited repair synthesis and ligation usually involving base pair deletions

Question 14

Ataxia telangiectasia is a disorder of which DNA repair pathway?

Answer 14

Homologous recombination

Question 15

BRCA1/2 dependent inherited cancers are disorders of which DNA repair pathway?

Answer 15

Homologous recombination

Question 16

Werner syndrome is a disorder of which DNA repair pathway?

Answer 16

Homologous recombination and crosslink repair

Question 17

Fanconi anemia is a disorder of which DNA repair pathway?

Answer 17

Non-homologous end joining

Question 18

Bloom syndrome is a disorder of which DNA repair pathway?

Answer 18

Non-homologous end joining

Question 19

What are the clinical manifestations of ataxia telangiectasia?

Answer 19

Ataxia (loss of control of body movements), telangiectasia (widening of veins), immunodeficiency, extreme sensitivity to radiation, predisposition to malignancy

Question 20

What is the mechanism of ataxia telangiectasia?

Answer 20

Mutation in ATM gene leads to inability to recognize dsDNA breaks, so repair complex is never recruited and cell can progress through the cell cycle with damaged DNA

Question 21

What is the mechanism of BRCA1/2 dependent inherited cancers?

Answer 21

BRCA 1/2 are part of homologous recombination repair complex; dsDNA repair is defective

Question 22

What are the clinical manifestations of Fancomi anemia?

Answer 22

Short stature, developmental abnormalities, bone marrow disorders, cancer (especially leukemia)

Question 23

What is the mechanism of Fancomi anemia?

Answer 23

Mutation in one of 12 possible FANC genes (regulate interstrand DNA crosslink repair)

Question 24

What are the clinical manifestations of Werner syndrome?

Answer 24

Short stature, premature aging, cancer

Question 25

What is the mechanism of Werner syndrome?

Answer 25

Mutation in WRN gene (DNA helicase used in homologous recombination and DNA replication)

Question 26

What are the clinical manifestation of Bloom syndrome?

Answer 26

Short stature, narrow face, skin sensitivity to sun, SLE-resembling butterfly rash, immunodeficiency, cancer (especially leukemia), possible intellectual disability

Question 27

What is the mechanism of Bloom syndrome?

Answer 27

Mutation in BLM gene (DNA helicase used in homologous recombination and DNA replication)