A conserved Hsp70 phosphorylation regulates cell cycle progression after DNA damage
Moss, T.; Wooldredge, A.; Bhakta, K.; Cronin, M.; Gestwicki, J. E.; Mukherjee, S.
10.1101/2025.09.05.672953 bioRxivShow abstract
Hsp70s are essential molecular chaperones that are increasingly recognized to be regulated by post-translational modifications. Here, we show that phosphorylation of a conserved threonine (T495), previously shown to be exploited by a Legionella pneumophila kinase to inhibit Hsp70, occurs endogenously in human cells in response to DNA damage, particularly when base excision repair is overburdened. This modification is cell cycle dependent, and in yeast, phosphomimetic or phosphonull Hsp70 variants disrupt G1/S progression under normal and DNA-damaging conditions. Biochemically, the phosphomimetic T495E mutation locks Hsp70 in an open-like conformation without blocking substrate engagement. Together, our results reveal a conserved mechanism by which dynamic Hsp70 phosphorylation regulates the G1/S transition, and delays cell cycle progression during DNA damage, highlighting how pathogen-derived insights can uncover fundamental cell biology principles.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- SDE2 Integrates into the TIMELESS-TIPIN Complex to Protect Stalled Replication Forks 96%
- The human RIF1-Long isoform interacts with BRCA1 to promote recombinational fork repair under DNA replication stress 96%
- The Fanconi anemia core complex promotes CtIP-dependent end-resection to drive homologous recombination at DNA double-strand breaks 96%
Similar papers in this journal
- RIF1-Long promotes G1 phase 53BP1 nuclear bodies to protect against replication stress 96%
- Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation 96%
- Live-cell single-molecule tracking highlights requirements for stable Smc5/6 chromatin association in vivo 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.