Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates

Michael H. Hauer, Andrew Seeber, Vijender Singh, Raphael Thierry, Ragna Sack, Assaf Amitai, Mariya Kryzhanovska, Jan Eglinger, David Holcman, Tom Owen-Hughes, Susan M. Gasser (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)
322 Downloads (Pure)

Abstract

Nucleosomes are essential for proper chromatin organization and the maintenance of genome integrity. Histones are post-translationally modified and often evicted at sites of DNA breaks, facilitating the recruitment of repair factors. Whether such chromatin changes are localized or genome-wide is debated. Here we show that cellular levels of histones drop 20-40% in response to DNA damage. This histone loss occurs from chromatin, is proteasome-mediated and requires both the DNA damage checkpoint and the INO80 nucleosome remodeler. We confirmed reductions in histone levels by stable isotope labeling of amino acids in cell culture (SILAC)-based mass spectrometry, genome-wide nucleosome mapping and fluorescence microscopy. Chromatin decompaction and increased fiber flexibility accompanied histone degradation, both in response to DNA damage and after artificial reduction of histone levels. As a result, recombination rates and DNA-repair focus turnover were enhanced. Thus, we propose that a generalized reduction in nucleosome occupancy is an integral part of the DNA damage response in yeast that provides mechanisms for enhanced chromatin mobility and homology search.

Original languageEnglish
Pages (from-to)99-107
Number of pages13
JournalNature Structural & Molecular Biology
Volume24
Issue number2
Early online date9 Jan 2017
DOIs
Publication statusPublished - Feb 2017

Keywords

  • Chromatin structure
  • DNA damage response
  • Genomic instability
  • Mass spectrometry
  • Microscopy

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