DNA damage detection in nucleosomes involves DNA register shifting

• Matsumoto, Syota

• Cavadini, Simone

• Bunker, Richard D.

• Grand, Ralph S.

• Potenza, Alessandro

• Rabl, Julius

• Yamamoto, Junpei

• Schenk, Andreas D.

• Schübeler, Dirk

• Iwai, Shigenori

• 菅澤, 薫

• Kurumizaka, Hitoshi

• Thomä, Nicolas H.

抄録

Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6–4 pyrimidine–pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA.

収録刊行物

• Nature

  Nature 571 79-84, 2019-05-29

  Nature Publishing Group

キーワード

• Multidisciplinary

詳細情報

• CRID: 1050012570392876032
• NII論文ID: 120006634977
• NII書誌ID: AA00752384
• DOI: 10.1038/s41586-019-1259-3
• ISSN: 14764687
• ISSN: 00280836
• HANDLE: 20.500.14094/90006047
• Web Site: http://www.nature.com/articles/s41586-019-1259-3.pdf
• Web Site: http://www.nature.com/articles/s41586-019-1259-3
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN