Induction of DNA double strand break by environmental genotoxic and carcinogenic agents

环境遗传毒性和致癌物质诱导 DNA 双链断裂

• 批准号: 18101002
• 负责人: KOMATSU Kenshi
• 金额: $ 69.56万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18101002/
• 关键词: DNA修復; 複製阻害; H2AXリン酸化; 環境変異原,NBS1; NBS1; DNA二重鎖切断; 損傷乗り越え合成; H2Bユビキチン化; クロマチンリモデリング; 環境変異原; DNA 修復; H2AX リン酸化; SMC1; 二重鎖切断; 放射線; 紫外線; DNA鎖架橋; 感興変異原; 多環芳香族炭化水素付加体; トポイソメレース阻害剤

By using phosphorylation of histone H2AX as a marker of DNA lesion, we showed here that DNA double strand breaks were generated by several environmental genotoxic and carcinogenic agents including UV and DNA cross-linking agents. These agents also induced gene mutations through translesional DNA synthesis, which is associated with NBS1. NBS1 is also involved in phosphorylation of H2AX and chromatin-remodeling at sites of DNA damage. Thus, NBS1 plays important roles in genome stability (inhibition of tumorigenesis) through DNA repair and cellular response to DNA lesions.

通过使用组蛋白H2AX的磷酸化作为DNA损伤的标志，我们在这里表明，DNA双链断裂产生的几种环境遗传毒性和致癌剂，包括紫外线和DNA交联剂。这些药物还通过与NBS1相关的跨病变DNA合成诱导基因突变。NBS1还参与H2AX的磷酸化和DNA损伤部位的染色质重塑。因此，NBS1通过DNA修复和对DNA损伤的细胞反应在基因组稳定性（抑制肿瘤发生）中起重要作用。

项目成果

Translesion DNA synthesis across mono ADP-ribosylated deoxyguanosine by Y-family DNA polymerases.

Y 家族 DNA 聚合酶跨单 ADP 核糖基化脱氧鸟苷进行跨损伤 DNA 合成。

• 发表时间: 2006
• 期刊: New Developments in Mutation Research 6
• 作者: Masuda;H.;M.Kawanishi
• 通讯作者: M.Kawanishi

Multiple roles of NBS1 in genome stability after genotoxic and non-genotixic stresses

NBS1 在基因毒性和非基因毒性应激后基因组稳定性中的多重作用

• 发表时间: 2008
• 作者: K.Arai;et al.;Kenshi Komatsu
• 通讯作者: Kenshi Komatsu

NBS1 foci formation and divergent roles in response to DNA damage-eliciting agents

NBS1 灶的形成和对 DNA 损伤诱发剂的不同作用

• 发表时间: 2006
• 作者: 新井邦明;福本恵紀;木下豊彦;ほか;Kenshi Komatsu
• 通讯作者: Kenshi Komatsu

Absence of Ku70 Gene Obliterates X-Ray-Induced lacZ Mutagenesis of Small Deletions in Mouse Tissues

• DOI: 10.1667/rr1283.1
• 发表时间: 2008-08
• 作者: Y. Uehara;H. Ikehata;J. Komura;A. Ito;Masaki Ogata;T. Itoh;R. Hirayama;Y. Furusawa;K. Ando;T. Paunesku;G. Woloschak;K. Komatsu;S. Matsuura;T. Ikura;K. Kamiya;T. Ono

Nijmegen breakage syndrome and functions of the responsible protein, NBS1

• DOI: 10.1159/000092508
• 发表时间: 2006-01-01
• 期刊: GENOME AND DISEASE
• 作者: Antoccia, A.;Kobayashi, J.;Komatsu, K.
• 通讯作者: Komatsu, K.