Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin.

ABSTRACT: Human genome stability requires efficient repair of oxidized bases, which is initiated via damage recognition and excision by NEIL1 and other base excision repair (BER) pathway DNA glycosylases (DGs). However, the biological mechanisms underlying detection of damaged bases among the million-fold excess of undamaged bases remain enigmatic. Indeed, mutation rates vary greatly within individual genomes, and lesion recognition by purified DGs in the chromatin context is inefficient. Employing super-resolution microscopy and co-immunoprecipitation assays, we find that acetylated NEIL1 (AcNEIL1), but not its non-acetylated form, is predominantly localized in the nucleus in association with epigenetic marks of uncondensed chromatin. Furthermore, chromatin immunoprecipitation followed by high-thro

SUBMITTER: Bacolla A 

PROVIDER: S-EPMC7797072 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature