DNA Mutation and Repair

Question 1

3 Steps of DNA Lesion Repair

Answer 1

1. Recognition: Lesion marked by protein binding and/or chromatin modification
   - ->PARP-1 Enzyme
2. Remove lesion
3. Fill in gap
   - ->Pol delta

Question 2

Nucleotide Mismatch Repair

Answer 2

small lesion

MMR mechanismn involves one single strand incision

Question 3

Base Excision Repair

Answer 3

small lesion, only base removed (not backbone)

1. DNA glycosylate binds to DNA
2. Endonuclease cleaves out lesion
3. DNA Pol and Ligase make correct DNA

Question 4

Lynch Syndrome

Answer 4

Elevated risk of colorectal cancer

->Congenital absence of 1 of the four proteins involved in DNA Mismatch Repair

Question 5

Pyrimidine Dimers

Answer 5

Complex DNA lesion
Corrected by Nucleotide Excision Repair by recognizing HELIX DISTORTING LESION
OR
Interstrand Cross Link Repair
->stops repication fork progression
->How cancer drug works

Question 6

Xeroderma Pigmentosum

Answer 6

Caused by failure of Nuclear Excision Repair mechanism to correct for Pyrimidine Dimers

Question 7

Fanconi’s Anemia Pathway

Answer 7

Failure of Interstrand-Crosslink Repair to correct Pyrimidine Dimers because of a loss of a protein involved AKA BRCA

-> Extra sensitive to mutations

Question 8

Homologous Recombination

Answer 8

Type of Double Strand Break Repair
Occurs only in S and G2 phases (when chromosomes lined up)
DNA chromosome with mutation “invades” healthy chromosome to use as a template
–>BRCA 1 and 2 involved

Question 9

Non-Homologous end joining

Answer 9

1 KU protein binds

2. KU activates protein Kinase
3. Kinase activates end processing
4. Ends filled inxx

Question 10

BRCA 1 and 2 with RAD51 DNA Repair:

Answer 10

Involved in Double Strand Break Repair.

–>help “pull back” healthy DNA so other chromosome can invade

Question 11

Poly (ADP-Ribose) polymerase 1

Answer 11

• Binds to lesions and ribosylates surrounding chromatin
• flags for repair mechanisms
• If PARP is inhibited it leads to DS breaks = cell death
• —>exploited for breast cancer treatment

Question 12

How are repair mechanisms exploited to treat disease?

Answer 12

Cancers lack a lot of normal pathways, so rely heavily on what pathways they do have. This means cancer cells are especially sensitive to the inhibition of normal pathways.