positive regulation of base-excision repair

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of base-excision repair. [GO_REF:0000058, GOC:ah, GOC:TermGenie, PMID:18973764]

Positive regulation of base-excision repair is a crucial cellular process that safeguards the integrity of DNA by enhancing the efficiency of removing damaged or modified bases. This intricate process involves a coordinated interplay of multiple proteins and enzymatic activities. Here's a detailed breakdown:

1. **Damage Recognition:** The process begins with the identification of damaged or modified bases within the DNA molecule. Specialized DNA glycosylases, each with specificity for a particular type of base damage, recognize and remove the damaged base, creating an apurinic/apyrimidinic (AP) site.

2. **AP Site Processing:** An AP endonuclease then cleaves the phosphodiester bond at the 5' end of the AP site, generating a single-strand break with a 3' hydroxyl group and a 5' deoxyribose phosphate (dRP) residue.

3. **Gap Filling and Ligation:** DNA polymerase β (Pol β) binds to the 5' dRP residue and removes it, creating a single-nucleotide gap. The gap is then filled by Pol β, using the undamaged strand as a template. Finally, DNA ligase seals the nick, restoring the integrity of the DNA strand.

4. **Regulation and Coordination:** The efficiency of base-excision repair is tightly regulated by a complex network of proteins, including:
- **PARP1:** Poly(ADP-ribose) polymerase 1 senses DNA damage and promotes the recruitment of repair proteins to the site of damage.
- **XPA:** Xeroderma pigmentosum group A protein, a component of the nucleotide excision repair (NER) pathway, can also interact with base-excision repair proteins, potentially facilitating coordination between these two pathways.
- **ATM and ATR:** Ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) kinases, central players in the DNA damage response, can activate downstream signaling pathways that regulate base-excision repair.

5. **Significance:** Efficient positive regulation of base-excision repair is essential for maintaining genomic stability and preventing the accumulation of mutations that can lead to cancer and other diseases. Disruptions in this process can have severe consequences for cell survival and overall health.'
"

Proteins (1)

Compounds (2)