Question 1

What types of DNA damage does base excision repair fix?

Accepted Answer

Base excision repair corrects small base damages caused by deamination, oxidation, or alkylation that occur spontaneously or result from environmental toxins. These chemical alterations create weak base pairs that cause mispairing and strand breakage during replication. BER restores the original base sequence using the complementary strand as a template, maintaining DNA integrity.

Question 2

How do DNA glycosylases recognize and remove damaged bases?

Accepted Answer

DNA glycosylases detect weak base pairs formed by modified bases and wedge apart neighboring base pairs to flip out the damaged base. This flip allows the enzyme to interact with all facets of the base for accurate identification. Upon recognition, the glycosylase cleaves the N-glycosidic bond between the modified base and deoxyribose, releasing the free base and creating a gap in the DNA helix.

Question 3

What is the role of AP endonuclease in base excision repair?

Accepted Answer

AP endonuclease recognizes the gap left after DNA glycosylase removes a damaged base. Along with phosphodiesterase, APE cuts the phosphodiester backbone within the polynucleotide chain at the abasic site. This cleavage prepares the DNA for the insertion of the correct base by DNA polymerase and subsequent sealing by DNA ligase.

Question 4

How does DNA polymerase β complete the base excision repair process?

Accepted Answer

DNA polymerase β fills the gap created by AP endonuclease by copying the correct base from the complementary strand at that position. The polymerase uses its associated AP-lyase activity to remove the deoxyribose phosphate. DNA ligase then seals the remaining nick to restore an intact, fully repaired DNA molecule.

Question 5

What is the difference between monofunctional and bifunctional DNA glycosylases?

Accepted Answer

Bifunctional glycosylases make an incision in the phosphodiester chain after removing the damaged base, producing a 5' or 3' phosphate. Monofunctional glycosylases only remove the base and depend on AP endonuclease to cleave the sugar-phosphate link, producing a 3'OH and 5' deoxyribophosphate. Both pathways ultimately lead to base restoration.

Question 6

What protein scaffolds the base excision repair machinery at the damage site?

Accepted Answer

Both DNA ligase III and DNA polymerase use the protein XRCC1 as a scaffold to bind the site of repair. XRCC1 coordinates the assembly and function of multiple BER enzymes at the lesion, ensuring efficient and accurate restoration of the damaged DNA sequence.

Question 7

How do mutations in base excision repair proteins affect cancer risk?

Accepted Answer

Mutations in BER pathway proteins can lead to various cancer types. For example, a mutation in the human glycosylase OGG1 is associated with increased risk for lung and pancreatic cancers. These mutations impair the cell's ability to repair oxidative base damage, allowing mutations to accumulate and promote tumorigenesis.

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