The chromatin remodeler p400 ATPase facilitates Rad51-mediated repair of DNA double-strand breaks

J Cell Biol. 2012 Dec 24;199(7):1067-81. doi: 10.1083/jcb.201205059.

Abstract

DNA damage signaling and repair take place in a chromatin context. Consequently, chromatin-modifying enzymes, including adenosine triphosphate-dependent chromatin remodeling enzymes, play an important role in the management of DNA double-strand breaks (DSBs). Here, we show that the p400 ATPase is required for DNA repair by homologous recombination (HR). Indeed, although p400 is not required for DNA damage signaling, DNA DSB repair is defective in the absence of p400. We demonstrate that p400 is important for HR-dependent processes, such as recruitment of Rad51 to DSB (a key component of HR), homology-directed repair, and survival after DNA damage. Strikingly, p400 and Rad51 are present in the same complex and both favor chromatin remodeling around DSBs. Altogether, our data provide a direct molecular link between Rad51 and a chromatin remodeling enzyme involved in chromatin decompaction around DNA DSBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Line
  • Chromatin Assembly and Disassembly
  • DNA Breaks, Double-Stranded*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Knockdown Techniques
  • Histones / metabolism
  • Humans
  • Phosphorylation
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Transport
  • RNA Interference
  • Rad51 Recombinase / metabolism*
  • Recombinational DNA Repair*
  • Replication Protein A / metabolism
  • Signal Transduction

Substances

  • DNA-Binding Proteins
  • Histones
  • RPA1 protein, human
  • Replication Protein A
  • RAD51 protein, human
  • Rad51 Recombinase
  • DNA Helicases
  • EP400 protein, human