HAT1 as a Lactyltransferase to Promote DNA Repair Through RPA1 Lactylation in Glioblastoma.

ABSTRACT: Glioblastoma multiforme (GBM) remains the most lethal primary brain tumor, owing to its aggressive nature and resistant to most of standard therapies, including radiation therapy. The glycolytic metabolic preference of cancer cells leads to the accumulation of lactate, a precursor for post-translational protein lactylation. While this modification is implicated in GBM, its mechanistic contribution to therapeutic resistance to radiation therapy is not well defined. Here, we identify histone acetyltransferase 1 (HAT1) as a candidate target for radiosensitization in GBM. We demonstrate that HAT1 acts as a lactyltransferase, directly catalyzing the lactylation of replication protein A1 (RPA1) at lysine 88 (K88). Furthermore, lactate drives the transcriptional upregulation of HAT1 via KAT2B-med

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12905578 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature