論文

査読有り
2018年7月5日

Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2

Molecular Cell
  • Martin R. Higgs
  • ,
  • Koichi Sato
  • ,
  • John J. Reynolds
  • ,
  • Shabana Begum
  • ,
  • Rachel Bayley
  • ,
  • Amalia Goula
  • ,
  • Audrey Vernet
  • ,
  • Karissa L. Paquin
  • ,
  • David G. Skalnik
  • ,
  • Wataru Kobayashi
  • ,
  • Minoru Takata
  • ,
  • Niall G. Howlett
  • ,
  • Hitoshi Kurumizaka
  • ,
  • Hiroshi Kimura
  • ,
  • Grant S. Stewart

71
1
開始ページ
25
終了ページ
41.e6
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.molcel.2018.05.018
出版者・発行元
Cell Press

Components of the Fanconi anemia and homologous recombination pathways play a vital role in protecting newly replicated DNA from uncontrolled nucleolytic degradation, safeguarding genome stability. Here we report that histone methylation by the lysine methyltransferase SETD1A is crucial for protecting stalled replication forks from deleterious resection. Depletion of SETD1A sensitizes cells to replication stress and leads to uncontrolled DNA2-dependent resection of damaged replication forks. The ability of SETD1A to prevent degradation of these structures is mediated by its ability to catalyze methylation on Lys4 of histone H3 (H3K4) at replication forks, which enhances FANCD2-dependent histone chaperone activity. Suppressing H3K4 methylation or expression of a chaperone-defective FANCD2 mutant leads to loss of RAD51 nucleofilament stability and severe nucleolytic degradation of replication forks. Our work identifies epigenetic modification and histone mobility as critical regulatory mechanisms in maintaining genome stability by restraining nucleases from irreparably damaging stalled replication forks.

リンク情報
DOI
https://doi.org/10.1016/j.molcel.2018.05.018
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29937342
ID情報
  • DOI : 10.1016/j.molcel.2018.05.018
  • ISSN : 1097-4164
  • ISSN : 1097-2765
  • PubMed ID : 29937342
  • SCOPUS ID : 85048563978

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