6.4 DNA Repair

Question 1

How do abnormal alleles lead to cell cycle advancement?

Answer 1

• encode proteins that are more active than normal proteins

Question 2

What genes participate in DNA repair processes?

Answer 2

• Tumor suppressor genes, like p53 or Rb (retinoblastoma)
• encode proteins that inhibit the cell cycle or participate in DNA repair processes
• Just one copy of the normal protein can function to inhibit tumor formation

Question 3

What happens when complementary strands have incorrectly paired bases?

Answer 3

• the hydrogen bonds between the strands can be unstable, and this lack of stability is detected as the DNA passes through this part of the polymerase.

Question 4

how does the enzyme discriminate which is the template strand, and which is the incorrectly paired daughter strand?

Answer 4

• It looks at the level of methylation: the template
  strand has existed in the cell for a longer period of time, and therefore is more heavily methylated. Methylation also plays a role in the transcriptional activity of DNA

Question 5

Why is the likelihood of mutations in the lagging strand considerably higher than the leading strand?

Answer 5

DNA ligase, which closes the gaps between Okazaki fragments, lacks proofreading ability

Question 6

What do enzymes encoded by MSH2 and MLH1 do?

Answer 6

• Do mismatch repair by detecting and removing errors introduced in replication that were missed during the S
  phase of the cell cycle

Question 7

How do the repair mechanisms work?

Answer 7

• Most involve proteins that recognize damage or a lesion, remove the damage, and then use the complementary strand as a template to fill in the gap

Question 8

What is Nucleotide Excision Repair mechanism and how is it triggered?

Answer 8

• UV light -> Thymine dimers (interfere with DNA rep., gene expression & distorts shape) -> distorts helix & messes up replication -> triggers NER mech.
• NER mech:
  1. Recog. damage (it’s a bulge)
  2. excision endonuclease (exinuclease) removes oligonulceotide
  3. DNA poly. synth 5’ to 3’ & ligase seals

Question 9

Base Excision Repair mechanism

Answer 9

Thermal energy -> cytosine to uracil -> glycosylase enzyme (rec. & remove) *leaves a -> AP site -> AP endonucl. removes damage -> DNA poly. rep. -> DNA ligase seals