HAT1 functions as a lactyltransferase and mediates RPA1 lactylation to promote DNA repair and radioresistance in lung adenocarcinoma.

ABSTRACT: Lysine lactylation is a post-translational modification induced by lactate discovered in recent years. Abnormal lysine lactylation contributes to the occurrence and progression of various tumors. However, the mediators and downstream targets of lysine lactylation remain unclear. Here, we report that HAT1 serves as a potential lactyltransferase that can promote homologous recombination and lead to radioresistance by regulating lactylation of RPA1. Lactylation of RPA1 facilitates its binding to single-stranded DNA and MRE11-RAD50-NBS1 (MRN) complexes and promotes homologous recombination. HAT1 knockout inhibits DNA repair in lung adenocarcinoma cells, thereby increasing radiotherapy sensitivity. Interestingly, we also found that K15 auto-lactylation of HAT1 can modulate its lactyltransferase

SUBMITTER: He J 

PROVIDER: S-EPMC12639135 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature