Molecular mechanisms of translesion DNA synthesis and its involvement in carcinogenesis

跨损伤DNA合成的分子机制及其参与致癌作用

• 批准号: 17013053
• 负责人: HANAOKA Fumio
• 金额: $ 115.58万
• 依托单位: Gakushuin University (2008-2009)Osaka University (2005-2007)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17013053/
• 关键词: がん; 遺伝子; ゲノム安定性; DNAポリメラーゼ; DNA修復; 損傷乗り越え複製; ノックアウトマウス; 紫外線; ミスマッチ修復; タンパク質構造; 癌; ゲノム; 分裂酵母; ユビキチン; DNAポリメラーゼ・イータ; REV1; 色素性乾皮症; DNAポリメラーゼ・イオタ; 複製フォーク停止; 色素性乾皮症バリアント

We have clarified the mechanism in which human DNA polymerase η (Polη) interacts with other proteins for switching between Polη and the replicative polymerase at stalled replication forks. We have solved high-resolution crystal structures of human Polη at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. In addition, we have generated Polηknockout mice and observed high incidence of skin tumors upon UV-B irradiation in these mice.

我们已经阐明了人类DNA聚合酶η（Polη）与其他蛋白质相互作用以在停滞的复制叉处在Polη和复制聚合酶之间切换的机制。我们通过顺式-顺式环丁烷胸腺嘧啶二聚体在DNA合成过程中的四个连续步骤中解决了人Polη的高分辨率晶体结构。此外，我们已经产生了Polη敲除小鼠，并且在这些小鼠中观察到UV-B照射后皮肤肿瘤的高发病率。

项目成果

Negative regulation of condensin I by CK2‐mediated phosphorylation

• DOI: 10.1038/sj.emboj.7601394
• 发表时间: 2006-11
• 期刊: The EMBO Journal
• 作者: Ai Takemoto;K. Kimura;J. Yanagisawa;S. Yokoyama;F. Hanaoka

A genome-wide survey and systematic RNAi-based characterization of helicase-like genes in Caenorhabditis elegans

• DOI: 10.1093/dnares/dsm016
• 发表时间: 2007-08-31
• 期刊: DNA RESEARCH
• 影响因子: 4.1
• 作者: Eki, Toshihiko;Ishihara, Takeshi;Hanaoka, Fumio
• 通讯作者: Hanaoka, Fumio

The chromosomal association of condensin II is required by a noncatalytic function of PP2A.

PP2A 的非催化功能需要凝缩蛋白 II 的染色体缔合。

• 发表时间: 2009
• 期刊: Nat.Struct.Aiol.Biol. 16
• 作者: Takemoto;A.;Maeshima;K.;Ikehara;T.;Yamaguchi;K.;Murayama;A.;Imamura;S.;lamamoto;N.;Yokoyama;S.;Hirano;T.;Watanabe;Y.;Hanaoka;F.;Yanagisawa;J.;Kimura;K.
• 通讯作者: K.

Tumorigenesis induced by chronic treatment with UV-B in Pol η- and Xpc-deficient mice.

Pol η 和 Xpc 缺陷小鼠长期接受 UV-B 治疗可诱导肿瘤发生。

• 发表时间: 2010
• 作者: Hanaoka;F.
• 通讯作者: F.

In Vivo Destabilization and Functional Defects of the Xeroderma Pigmentosum C Protein Caused by a Pathogenic Missense Mutation

• DOI: 10.1128/mcb.02166-06
• 发表时间: 2007-08
• 期刊: Molecular and Cellular Biology
• 影响因子: 5.3
• 作者: Gentaro Yasuda;Ryotaro Nishi;Eriko Watanabe;Toshio Mori;S. Iwai;D. Orioli;M. Stefanini;F. Hanaoka;K. Sugasawa