DNA Damage

Question 1

Transition Mutation?

Answer 1

PurinePurine, PyrimidinePyrimidine mutation

Question 2

Transversion Mutation?

Answer 2

PurinePyrimidine

Question 3

What are tautomeric shifts and what do they cause?

Answer 3

G/T: KetoEnol
A/C: AminoImino
Cause DNA replication errors (:o)

Question 4

What damage does UVB cause? Wavelengths?

Answer 4

Cross-links adjacent C+T bases aka pyrimidine dimers (direct damage). 315-280 nm.

Question 5

What damage does UVA cause? Wavelengths?

Answer 5

Free radicals (indirect damage). 400-315 nm.

Question 6

What damage does ionizing radiation cause? What are sources?

Answer 6

DNA breaks. x-rays, gamma rays, cosmic rays.

Question 7

What damage does thermal disruption cause?

Answer 7

Depurination, Single strand breaks

Question 8

What damage do industrial/environmental chemicals cause?

Answer 8

DNA adducts, cross-linking

Question 9

What does the Ames test measure?

Answer 9

If a substance is mutagenic (carcinogenic) based on if it mutates bacteria to use histidine.

Question 10

What is the DNA repair method of last resort, and when do you use it?

Answer 10

Translesion synthesis, when the complementary strand/homologous chromosome is unavailable.

Question 11

What does MGMT do? What is the process?

Answer 11

Deakylate O6-alkyl guanine (direct repair)

Question 12

How is UV-induced damage corrected in bacteria? Mammals?

Answer 12

Photoreactivation reaction with sunlight and 4-photolyase; nucleotide excision repair

Question 13

What enzymes are used in base excision repair?

Answer 13

Glycosidases and endonucleases

Question 14

What damage does NER fix?

Answer 14

thymine dimers (UV) and large adducts

Question 15

Defects in NER can lead to what autosomal recessive disorder?

Answer 15

Xeroderma Pigmentosum; hypersensitivity to sunlight

Question 16

What repair process corrects replication errors? What disease is characteristic of defects in this process?

Answer 16

Mismatch repair; heriditary nonpolyposis colon

Question 17

What response to dsDNA damage occurs in G1/S phase? What is negative about this process?

Answer 17

NEJ, non-homologous end-joining; can introduce mutations, cause deletions and translocations

Question 18

What is required for homologous recombination? What cell cycle stage is it used?

Answer 18

The presence of an identical or nearly identical sequence to be used as a TEMPLATE; G2 after replication

Question 19

What is defective in xeroderma pigmentosum?

Answer 19

NER

Question 20

What genes are mutated in Li Faumeni? What are they involved in?

Answer 20

p53 and chk2; detection of DNA damage to prevent entry to S phase

Question 21

What disease involves a Ser/Thr kinase involved in signal transduction of DNA damage signals?

Answer 21

Ataxia-Telogiectasia (AT)

ATM gene

Question 22

What gene is mutated in Nijmegon Breakage Syndrome? What is this gene a part of?

Answer 22

NBS1 Gene; the MRN complex used in dsDNA break repair through homologous recombination

Question 23

What is the defect in Fanconi anemia?

Answer 23

Inability to repair interstrand DNA cross-links

Translesional synthesis

Question 24

What syndromes are caused by mutations in RECQ helicase? What is the defect?

Answer 24

Blooms + Werner; Hyperrecombination + defects in dsDNA break repair

Question 25

What genes are implicated in breast and ovarian cancer susceptibility? What are they involved in?

Answer 25

BRCA1 + BRCA2; DSB repair (scaffolds)

Question 26

What causes hereditary non-polyposis colorectal cancer?

Answer 26

Mutations in DNA mismatch repair genes

Question 27

What disease is caused by mutations in the APC gene?

Answer 27

FAP (familial adenomatous colon cancer)