C8orf33 dictates DNA double-strand break repair choice by modulating KAT8-mediated H4K16 acetylation.

ABSTRACT: Homologous recombination (HR) and non-homologous end joining (NHEJ) are two main repair pathways of DNA double-strand breaks (DSBs). The regulation of repair pathway choice is crucial for maintaining genomic stability and preventing carcinogenesis. Consequently, there is increasing interest in elucidating the molecular mechanisms that govern DSB repair pathway selection. Here, we identify chromosome 8 open reading frame 33 (C8orf33) as a novel regulator of DSB repair choice. We show that C8orf33 is a nuclear protein localized predominantly to the nucleolus and is recruited to DSB sites within both nuclear and nucleolar regions. We demonstrate that C8orf33 promotes the recruitment of 53BP1, thus channeling DSB repair toward NHEJ. Consequently, C8orf33 inhibits DNA end resection and countera

SUBMITTER: Bishara LA 

PROVIDER: S-EPMC12624059 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature