ゲノムネットワークプロジェクト

個別生命機能の解析
研究課題 蛋白の可視化と機能的複合体解析で解くゲノム安定性ネットワーク
研究期間 平成18年度〜20年度
研究課題代表者 安井 明
所属機関 東北大学 加齢医学研究所
研究目的 活性酸素などで生じるゲノム損傷は複製や転写に重大な影響を与え、ゲノム不安定性を産み、癌や遺伝病のそもそもの原因となり、老化や神経疾患をももたらす。この研究の目的は、蛋白質の可視化とプロテオミクスを融合した新しい解析技術を用いて、ヒト細胞でのゲノム安定性を担う新規の蛋白複合体の機能的ネットワークを明らかにし、ゲノム疾患の診断、治療、予防に貢献することである
研究概要 ①転写抑制因子ポリコームmPcl1/hPHF1蛋白がp53やKUと相互作用し、二重鎖切断の修復での機能を発見(NAR2008)。②ヒト塩基喪失部位の修復を行なうAPエンド/エキソヌクレアーゼPALFを発見。PARP1を活性化し、単鎖切断と二重鎖切断の修復に関わる(EMBOJ 2007)。③ウエルナー早老症の原因蛋白質WRNが損傷乗り越えの複製(TLS)に働く事を発見 (PNAS2007)。④転写制御因子のクロマチン蛋白HMGB1が活性酸素損傷の修復に関わる (Mol Cell 2007)。
研究成果 ①転写抑制因子ポリコームmPcl1/hPHF1蛋白がp53やKUと相互作用し、二重鎖切断の修復での機能を発見(NAR2008)。②ヒト塩基喪失部位の修復を行なうAPエンド/エキソヌクレアーゼPALFを発見。PARP1を活性化し、単鎖切断と二重鎖切断の修復に関わる(EMBOJ 2007)。③ウエルナー早老症の原因蛋白質WRNが損傷乗り越えの複製(TLS)に働く事を発見 (PNAS2007)。④転写制御因子のクロマチン蛋白HMGB1が活性酸素損傷の修復に関わる (Mol Cell 2007)。
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研究論文・特許出願・
学術発表など
------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:600
PUBLICATION TYPE: journal
PUBLICATION NAME: Nucleic Acids Research
ARTICLE TITLE: Recruitment of DNA repair synthesis machinery to sites of DNA damage/repair in living human cells
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-03-15
TITLE: Recruitment of DNA repair synthesis machinery to sites of DNA damage/repair in living human cells
STATUS: Published
AUTHOR NAME: Kazunari Hashiguchi1*, Yoshihiro Matsumoto2 and Akira Yasui1*
AUTHOR AFFILIATION: 1Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan, and 2Division of Medical Science, Fox Chase Cancer Center, PA 19111

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:621
PUBLICATION TYPE: journal
PUBLICATION NAME: EMBO Journal
ARTICLE TITLE: A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-05-01
TITLE: A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses
STATUS: Published
AUTHOR NAME: 1, 2, 3Shin-ichiro Kanno, 1Hiroyuki Kuzuoka, 1Shigeru Sasao, 1Zehui Hong, 1Li Lan, 1Satoshi Nakajima and 1, 3,4Akira Yasui
AUTHOR AFFILIATION: 1Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aobaku, Sendai 980-8575, Japan, and 2Japan Bio Services Co., Ltd., Asaka, Saitama 351-0011, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:690
PUBLICATION TYPE: journal
PUBLICATION NAME: Proc Natl Acad Sci U S A.
ARTICLE TITLE: The Werner syndrome protein interacts functionally with translesion DNA synthesis.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-06-19
TITLE: The Werner syndrome protein interacts functionally with translesion DNA synthesis.
STATUS: Published
AUTHOR NAME: Kamath-Loeb, A.S., Li, L., Nakajima, S., Yasui, A., and Loeb L.L.
AUTHOR AFFILIATION: Department of Pathology, The Gottstein Memorial Cancer Research Center, University of Washington, Seattle, WA 98195, USA; Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryomachi 4-1, Aobaku, Sendai 98-8575, Japan.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:691
PUBLICATION TYPE: journal
PUBLICATION NAME: Mol Cell
ARTICLE TITLE: HMGB1 is a co-factor in mammalian base excision repair.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-08-10
TITLE: HMGB1 is a co-factor in mammalian base excision repair.
STATUS: Published
AUTHOR NAME: Prasad, R, Liu, Y, Deterding, LJ, Poltoratsky, VP, Kedar, PS, Horton, JK, Kannno, S.-I, Asagoshi, K, Hou, EW, Khodyreva, SN, Lavrik, OI, Tomer. KB, Yasui, A, and Wilson, SH.
AUTHOR AFFILIATION: Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, Russia

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1273
PUBLICATION TYPE: journal
PUBLICATION NAME: Nucleic Acids Research
ARTICLE TITLE: A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-05-01
TITLE: A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell
STATUS: Published
AUTHOR NAME: 1Zehui Hong, 1Jie Jiang, 1Li Lan, 1Satoshi Nakajima, 1Shin-ichiro Kanno, 2Haruhiko Koseki and 1*Akira Yasui
AUTHOR AFFILIATION: 1Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryomachi 4-1, Aobaku, Sendai 980-8575, Japan, . 2Laboratory of Developmental Genetics, Riken Research Center for Allergy and Immunology, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama 230-0045, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1597
PUBLICATION TYPE: journal
PUBLICATION NAME: Journal of Cell Science
ARTICLE TITLE: Recruitment of mismatch repair proteins to the site of DNA damage in human cells
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-07-25
TITLE: Recruitment of mismatch repair proteins to the site of DNA damage in human cells
STATUS: Published
AUTHOR NAME: Zehui Hong, Jie Jiang, Kazunari Hashiguchi, Mikiko Hoshi, Li Lan and *Akira Yasui
AUTHOR AFFILIATION: Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1798
PUBLICATION TYPE: journal
PUBLICATION NAME: Molecular and Cellular Biology
ARTICLE TITLE: Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80.
SUBMIT DATE: 2008-08-01
ACCEPT DATE: 2008-12-20
PUBLICATION DATE: 2009-03-01
TITLE: 蛋白の可視化と機能的複合体解析で解くゲノム安定性ネットワーク
STATUS: Published
AUTHOR NAME: Wei L, Lan L, Hong Z, Yasui A, Ishioka C, Chiba N.
AUTHOR AFFILIATION: Department of Clinical Oncology, and Department of Molecular Genetics, Institute of Development, Aging and Cancer (IDAC), Tohoku University 4-1 Seiryomachi Aoba-ku Sendai 980-8575, Japan.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1799
PUBLICATION TYPE: journal
PUBLICATION NAME: EMBO Journal
ARTICLE TITLE: Human DNA polymerase iota protects cells against oxidative stress.
SUBMIT DATE: 2008-05-20
ACCEPT DATE: 2008-10-15
PUBLICATION DATE: 2009-03-05
TITLE: 蛋白の可視化と機能的複合体解析で解くゲノム安定性ネットワーク
STATUS: Published
AUTHOR NAME: Petta TB, Nakajima S, Zlatanou A, Despras E, Couve-Privat S, Ishchenko A, Sarasin A, Yasui A, Kannouche P.
AUTHOR AFFILIATION: Centre National de la Recherche Scientifique FRE2939, Unit of genetic stability and oncogenesis, Institut Gustave Roussy, Université Paris-Sud, Villejuif, France, Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Japan

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