Unfilled gaps by polβ lead to aberrant ligation by LIG1 at the downstream steps of base excision repair pathway.

ABSTRACT: Base excision repair (BER) involves the tightly coordinated function of DNA polymerase β (polβ) and DNA ligase I (LIG1) at the downstream steps. Our previous studies emphasize that defective substrate-product channeling, from gap filling by polβ to nick sealing by LIG1, can lead to interruptions in repair pathway coordination. Yet, the molecular determinants that dictate accurate BER remains largely unknown. Here, we demonstrate that a lack of gap filling by polβ leads to faulty repair events and the formation of deleterious DNA intermediates. We dissect how ribonucleotide challenge and cancer-associated mutations could adversely impact the ability of polβ to efficiently fill the one nucleotide gap repair intermediate which subsequently results in gap ligation by LIG1, leading to the forma

SUBMITTER: Gulkis M 

PROVIDER: S-EPMC11039997 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature