NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.

ABSTRACT: The Warburg effect is a hallmark of cancer that refers to the preference of cancer cells to metabolize glucose anaerobically rather than aerobically^1,2. This results in substantial accumulation of lacate, the end product of anaerobic glycolysis, in cancer cells³. However, how cancer metabolism affects chemotherapy response and DNA repair in general remains incompletely understood. Here we report that lactate-driven lactylation of NBS1 promotes homologous recombination (HR)-mediated DNA repair. Lactylation of NBS1 at lysine 388 (K388) is essential for MRE11-RAD50-NBS1 (MRN) complex formation and the accumulation of HR repair proteins at the sites of DNA double-strand breaks. Furthermore, we identify TIP60 as the NBS1 lysine lactyltransferase and the 'writer' of NBS1 K3

SUBMITTER: Chen H 

PROVIDER: S-EPMC11254748 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature