NUDT16 enhances the resistance of cancer cells to DNA-damaging agents by regulating replication fork stability via reversing HMGA1 ADP-ribosylation.

ABSTRACT: Precise DNA replication is the basis for maintaining cell proliferation and genome stability. Current chemotherapy drugs and radiotherapy induce cell death by aggravating replication stress, albeit with poor efficacy. The replication stress response has been shown to play fundamental roles in resistance to radiotherapy and chemotherapy. High mobility group A1 (HMGA1) promotes tumor progression by regulating autophagy, angiogenesis, and chemoresistance; however, its role in coordinating replication stress and cell cycle progression remains elusive. Our results indicated that HMGA1 recruited FANCD2 to promote DNA replication and cell cycle progression both by attenuating R-loop-induced replication stress and by protecting stalled replication forks from degradation, ultimately enhancing tumor

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12151214 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature