Identification of a chaperone-code responsible for Rad51-mediated genome repair

Khushboo Rani, Akanksha Gotmare, Andreas Maier, Ruchira Menghal, Nashat Akhtar, Nupur Fangaria, Johannes Buchner, Sunanda Bhattacharyya

Research output: Contribution to journalArticlepeer-review


Posttranslational modifications of Hsp90 are known to regulate its in vivo chaperone functions. Here, we demonstrate that the lysine acetylation-deacetylation dynamics of Hsp82 is a major determinant in DNA repair mediated by Rad51. We uncover that the deacetylated lysine 27 in Hsp82 dictates the formation of the Hsp82-Aha1-Rad51 complex, which is crucial for client maturation. Intriguingly, Aha1-Rad51 complex formation is not dependent on Hsp82 or its acetylation status; implying that Aha1-Rad51 association precedes the interaction with Hsp82. The DNA damage sensitivity of Hsp82 (K27Q/K27R) mutants are epistatic to the loss of the (de)acetylase hda1Δ; reinforcing the importance of the reversible acetylation of Hsp82 at the K27 position. These findings underscore the significance of the cross talk between a specific Hsp82 chaperone modification code and the cognate cochaperones in a client-specific manner. Given the pivotal role that Rad51 plays during DNA repair in eukaryotes and particularly in cancer cells, targeting the Hda1-Hsp90 axis could be explored as a new therapeutic approach against cancer.

Original languageEnglish
Article number107342
JournalJournal of Biological Chemistry
Issue number6
StatePublished - Jun 2024


  • DNA repair
  • Saccharomyces cerevisiae
  • chaperone
  • heat shock protein 90 (Hsp90)
  • homologous recombination
  • proteostasis


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