Mechanisms of Centrosome Aberrations Induced by DNA damage

DNA损伤引起中心体畸变的机制

• 批准号: 21310034
• 负责人: MIYAGAWA Kiyoshi
• 金额: $ 11.81万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21310034/
• 关键词: DNA損傷; 中心体; 相同組換え; 染色体不安定性; 放射線発がん

Maintenance of centrosome numbers is required for correct chromosome segregation, and radiation induces its aberrations. In order to understand their mechanisms, we investigated roles of the DNA damage response in maintenance of centrosome integrity. We found that activation of the signaling pathway mediated by ATR and Chk1 causes supernumerary centrosomes when homologous recombination repair is inhibited. Supernumerary centrosomes are frequently observed in cancer. We also found that activation of ATM is involved in centrosome aberrations when SYCE2, a cancer testis antigen, is expressed. Additionally, aneuploidy is induced by centrosome-independent mechanisms in cells defective in homologous recombination repair, indicating that multiple pathways are involved in regulation of chromosome integrity.

正确的染色体分离需要维持中心体数，并且辐射引起其畸变。为了了解其机制，我们研究了DNA损伤响应在维持中心体完整性中的作用。我们发现，当抑制同源重组修复时，由ATR和CHK1介导的信号通路的激活会导致超整体中心体。在癌症中经常观察到上心颗粒。我们还发现，当表达Syce2（一种癌症抗原）时，ATM的激活与中心体畸变有关。另外，非整倍性是由与同源重组修复中缺陷的细胞中心体无关的机制诱导的，表明多个途径参与调节染色体完整性。

项目成果

The synaptonemal complex protein SYCE2 induces chromosome instability through activation of ATM in cancer

联会复合体蛋白 SYCE2 通过激活癌症中的 ATM 诱导染色体不稳定

• 发表时间: 2011
• 作者: 柴田康行;吉兼光葉;Hosoya N
• 通讯作者: Hosoya N

Serine-Threonine Kinase 38 is regulated by Glycogen Synthase Kinase-3 and modulates oxidative stress-induced cell death

• DOI: 10.1016/j.freeradbiomed.2011.11.006
• 发表时间: 2012-01-15
• 期刊: FREE RADICAL BIOLOGY AND MEDICINE
• 影响因子: 7.4
• 作者: Enomoto, Atsushi;Kido, Naoki;Miyagawa, Kiyoshi
• 通讯作者: Miyagawa, Kiyoshi

DNA損傷修復の核ダイナミクス

DNA损伤修复的核动力学

• 发表时间: 2009
• 作者: 宮川清

The synaptonemal complex protein SYCE2 induces chromosome instability in mitotic cells through activation of the ataxia-telangiectasia-mutated kinase

联会复合体蛋白 SYCE2 通过激活共济失调毛细血管扩张突变激酶诱导有丝分裂细胞染色体不稳定

• 发表时间: 2011
• 作者: Hosoya N;Miyagawa K
• 通讯作者: Miyagawa K