UV damage-induced phosphorylation of HBO1 triggers CRL4DDB2-mediated degradation to regulate cell proliferation

• Material Type: 博士論文
• Title: UV damage-induced phosphorylation of HBO1 triggers CRL4DDB2-mediated degradation to regulate cell proliferation
• Volume: 38 3
• Author/Editor: Matsunuma, Ryoichi
• Author Heading: Matsunuma, Ryoichi
• Publication, Distribution, etc.: American Society for Microbiology
• Publication Date: 2016-02
• Publication Date (W3CDTF): 2016-02
• Alternative Title: 紫外線損傷により誘導されるHBO1のリン酸化はCRL4DDB2による分解のトリガーとなり細胞増殖を調整する
• Periodical title: Molecular and Cellular Biology
• Degree grantor/type: 浜松医科大学
• Date Granted: 2016-07-22
• Date Granted (W3CDTF): 2016-07-22
• Dissertation Number: 甲第733号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第733号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; Histone acetyltransferase binding to ORC-1 (HBO1) is a critically important histone acetyltransferase for forming the prereplicative complex (pre-RC) at the replication origin. Pre-RC formation is completed by loading of the MCM2-7 heterohexameric complex, which functions as a helicase in DNA replication. HBO1 recruited to the replication origin by CDT1 acetylates histone H4 to relax the chromatin conformation and facilitates loading of the MCM complex onto replication origins. However, the acetylation status and mechanism of regulation of histone H3 at replication origins remain elusive. HBO1 positively regulates cell proliferation under normal cell growth conditions. Whether HBO1 regulates proliferation in response to DNA damage is poorly understood. In this study, we demonstrated that HBO1 was degraded after DNA damage to suppress cell proliferation. Ser50 and Ser53 of HBO1 were phosphorylated in an ATM/ATR DNA damage sensor-dependent manner after UV treatment. ATM/ATR-dependently phosphorylated HBO1 preferentially interacted with DDB2 and was ubiquitylated by CRL4DDB2. Replacement of endogenous HBO1 in Ser50/53Ala mutants maintained acetylation of histone H3K14 and impaired cell cycle regulation in response to UV irradiation. Our findings demonstrate that HBO1 is one of the targets in the DNA damage checkpoint. These results show that ubiquitin-dependent control of the HBO1 protein contributes to cell survival during UV irradiation.
• DOI: info:doi/10.1128/MCB.00809-15; https://doi.org/info:doi/10.1128/MCB.00809-15
• Persistent ID (NDL): info:ndljp/pid/10371923; https://dl.ndl.go.jp/pid/10371923
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-07-03T04:10:06+09:00
• Date Created (W3CDTF): 2018-08-27
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/3199; https://hama-med.repo.nii.ac.jp/records/3055
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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