2. Academic Validation
  3. Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair

Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair

  • Nat Commun. 2017 Jul 18;8:16102. doi: 10.1038/ncomms16102.
Hiroyuki Niida 1,  Ryoichi Matsunuma 1 2,  Ryo Horiguchi 3,  Chiharu Uchida 3,  Yuka Nakazawa 4,  Akira Motegi 5,  Koji Nishimoto 1,  Satoshi Sakai 1,  Tatsuya Ohhata 1,  Kyoko Kitagawa 1,  Shinichi Moriwaki 6,  Hideo Nishitani 7,  Ayako Ui 8 9 10,  Tomoo Ogi 11,  Masatoshi Kitagawa 1 12
Affiliations

Affiliations

  • 1 Department of Molecular Biology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
  • 2 First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
  • 3 Advanced Research Facilities and Services, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
  • 4 Department of Genome Repair, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
  • 5 Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
  • 6 Department of Dermatology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
  • 7 Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori, Ako-gun, Hyogo 678-1297, Japan.
  • 8 Department of Translational Oncology, St Marianna University, School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki 216-8511, Japan.
  • 9 Institute of Medical Science, St Marianna University, School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki 216-8511, Japan.
  • 10 Department of Genome Regulation and Molecular Pharmacogenomics, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakuramachi, Hachioji, Tokyo 192-0983, Japan.
  • 11 Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
  • 12 Laboratory Animal Facilities and Services, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
PMID: 28719581 DOI: 10.1038/ncomms16102
Abstract

HBO1, a histone acetyl transferase, is a co-activator of DNA pre-replication complex formation. We recently reported that HBO1 is phosphorylated by ATM and/or ATR and binds to DDB2 after ultraviolet irradiation. Here, we show that phosphorylated HBO1 at cyclobutane pyrimidine dimer (CPD) sites mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites. Furthermore, HBO1 facilitates accumulation of SNF2H and ACF1, an ATP-dependent chromatin remodelling complex, to CPD sites. Depletion of HBO1 inhibited repair of CPDs and sensitized cells to ultraviolet irradiation. However, depletion of HBO1 in cells derived from xeroderma pigmentosum patient complementation groups, XPE, XPC and XPA, did not lead to additional sensitivity towards ultraviolet irradiation. Our findings suggest that HBO1 acts in concert with SNF2H-ACF1 to make the chromosome structure more accessible to canonical nucleotide excision repair factors.

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