The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication

Science. 2022 Mar 18;375(6586):1281-1286. doi: 10.1126/science.abm5320. Epub 2022 Mar 17.

Abstract

The tail of replication-dependent histone H3.1 varies from that of replication-independent H3.3 at the amino acid located at position 31 in plants and animals, but no function has been assigned to this residue to demonstrate a unique and conserved role for H3.1 during replication. We found that TONSOKU (TSK/TONSL), which rescues broken replication forks, specifically interacts with H3.1 via recognition of alanine 31 by its tetratricopeptide repeat domain. Our results indicate that genomic instability in the absence of ATXR5/ATXR6-catalyzed histone H3 lysine 27 monomethylation in plants depends on H3.1, TSK, and DNA polymerase theta (Pol θ). This work reveals an H3.1-specific function during replication and a common strategy used in multicellular eukaryotes for regulating post-replicative chromatin maturation and TSK, which relies on histone monomethyltransferases and reading of the H3.1 variant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics*
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Polymerase theta
  • DNA Repair*
  • DNA Replication*
  • DNA, Plant / metabolism*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Genome, Plant
  • Genomic Instability
  • Histones / chemistry
  • Histones / metabolism*
  • Lysine / metabolism
  • Methylation
  • Methyltransferases / genetics
  • Mutation
  • Protein Interaction Domains and Motifs

Substances

  • Arabidopsis Proteins
  • DNA, Plant
  • Histones
  • ATXR5 protein, Arabidopsis
  • ATXR6 protein, Arabidopsis
  • Methyltransferases
  • DNA-Directed DNA Polymerase
  • Lysine