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 损伤的标记，我们在此表明​​ DNA 双链断裂是由几种环境遗传毒性和致癌剂（包括紫外线和 DNA 交联剂）产生的。这些药物还通过跨病灶 DNA 合成诱导基因突变，这与 NBS1 相关。 NBS1 还参与 H2AX 的磷酸化和 DNA 损伤位点的染色质重塑。因此，NBS1 通过 DNA 修复和细胞对 DNA 损伤的反应在基因组稳定性（抑制肿瘤发生）中发挥重要作用。

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.