DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network

Colin M. Hammond, Hongyu Bao, Ivo A. Hendriks, Massimo Carraro, Alberto García-Nieto, Yanhong Liu, Nazaret Reverón-Gómez, Christos Spanos, Liu Chen, Juri Rappsilber, Michael L. Nielsen, Dinshaw J. Patel*, Hongda Huang, Anja Groth

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

From biosynthesis to assembly into nucleosomes, histones are handed through a cascade of histone chaperones, which shield histones from non-specific interactions. Whether mechanisms exist to safeguard the histone fold during histone chaperone handover events or to release trapped intermediates is unclear. Using structure-guided and functional proteomics, we identify and characterize a histone chaperone function of DNAJC9, a heat shock co-chaperone that promotes HSP70-mediated catalysis. We elucidate the structure of DNAJC9, in a histone H3-H4 co-chaperone complex with MCM2, revealing how this dual histone and heat shock co-chaperone binds histone substrates. We show that DNAJC9 recruits HSP70-type enzymes via its J domain to fold histone H3-H4 substrates: upstream in the histone supply chain, during replication- and transcription-coupled nucleosome assembly, and to clean up spurious interactions. With its dual functionality, DNAJC9 integrates ATP-resourced protein folding into the histone supply pathway to resolve aberrant intermediates throughout the dynamic lives of histones.

Original languageEnglish
Pages (from-to)2533-2548.e9
Number of pages16
JournalMolecular Cell
Volume81
Issue number12
Early online date14 Apr 2021
DOIs
Publication statusPublished - 17 Jun 2021

Keywords

  • chromatin replication
  • DNAJC9
  • heat shock co-chaperone
  • histone chaperone
  • HSP40
  • HSP70
  • MCM2
  • nucleosome assembly
  • TONSL
  • transcription

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