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11/24 臨床研セミナーのお知らせ


日時:平成17年11月24日(木)16:30 - 18:00

場所:東京都臨床医学総合研究所 2階会議室
JR「田端駅」下車 徒歩12分
地下鉄南北線「本駒込駅」下車 徒歩12分

演題:S-phase Checkpoint Responses to DNA Damage and Aberrant Replication Licensing

演者: Cyrus Vaziri&s_comma; Dept. of Genetics and Genomics&s_comma; Boston University
School of Medicine

Vaziri博士は、DNA損傷あるいは複製阻害により誘導されるS期チェックポイント機構について精力的に仕事をすすめておられます。また最近、Cdt1増産によるoverexpressionがp53経路により阻害されることを報告されています(Mol. Cell 11:997-1008&s_comma; 2003)。京都でのシンポジウムに招聘されたこの機会に最新の知見についてセミナーをしていただくことにしました。

S-phase checkpoints are activated in response to genotoxins and replication stress. The resulting signal transduction pathways inhibit initiation of DNA synthesis at unfired origins of DNA replication and stabilize stalled replication forks. We have investigated the roles of S-phase checkpoint signaling in mediating cellular responses to: (1) genotoxic damage induced by the environmental carcinogen Benzo[a]pyrene (B[a]P)&s_comma; and (2) replication stresses induced by imbalance between the replication licensing factor Cdt1 and its inhibitor geminin.

(1) We have shown that the Trans-Lesion Synthesis (TLS) DNA Polymerase Polκ is recruited to replication forks in B[a]P-treated cells&s_comma; and that Polκ-mediated lesion bypass is necessary for attenuation of checkpoint signaling. The role of the Rad18/Rad6 epistasis pathway and of ATR/Chk1 signaling in Polκ regulation will be discussed.

(2) We showed previously that aberrant Cdt1 activity (resulting from Cdt1 over-expression or down-regulation of geminin) results in over-replication of the genome in certain cancer cells. The role of p53 and Chk1-mediated checkpoint signaling in restricting DNA synthesis to once-per-cell-cycle will be discussed.

Tel: 03-5685-2264; Fax: 03-5685-2932
E-mail: hmasai@rinshoken.or.jp