Cooperation and interplay between base and nucleotide excision repair pathways: From DNA lesions to proteins

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Base excision repair (BER) and nucleotide excision repair (NER) traditionally handle distinct DNA damage types.
• BER targets small base modifications (e.g., oxidation), while NER addresses bulky lesions (e.g., UV, chemical carcinogens).
• Emerging evidence reveals significant crosstalk and protein exchange between BER and NER pathways.

Purpose of the Study:

• To review the complex interplay between BER and NER pathways.
• To highlight the involvement of NER in oxidative DNA damage repair.
• To discuss BER's role in removing bulky DNA adducts.

Main Methods:

• Literature review of studies on BER and NER pathway interactions.
• Analysis of experimental data, including UVA light-induced protein oxidation.
• Presentation of a protein interactome for BER and NER.

Main Results:

• NER participates in repairing oxidative DNA damage.
• BER is involved in removing bulky DNA adducts.
• Oxidative stress, exacerbated by UVA light, oxidizes BER and NER proteins, impairing DNA repair capacity.
• Protein oxidation in BER and NER components leads to mutagenesis, cell death, cancer, and aging.

Conclusions:

• BER and NER pathways exhibit complex cooperation beyond their canonical roles.
• Oxidative stress poses a significant threat by compromising both pathways.
• The identified protein interactome underscores the interconnectedness of BER and NER, suggesting shared functions crucial for genome stability.