Mechanisms of the signal transduction machinery in response to spontaneous DNA damage in human cells

信号转导机制响应人体细胞自发 DNA 损伤的机制

• 批准号: 18310037
• 负责人: MIYAGAWA Kiyoshi
• 金额: $ 11.51万
• 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: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18310037/
• 关键词: DNA damage; damage response; chromosome; DNA replication; radiation

It is important to understand cellular phenotypes that respond to spontaneously arising DNA damage without exogenous DNA damage. We have examined the effect of altered homologous recombination function on cell functions from the viewpoint of chromosome instability. Because Rad51B and XRCC3 play a role in homologous recombination in concert with Rad51, we used the human colon cancer cell line in which these genes were knocked out. We have shown that Rad51B prevents the generation of aneuploidy by stabilizing the centrosome. We previously showed that XRCC3 prevents chromosome duplication. Increased Cdt1 stability and increased accumulation of Cdc6 in the nucleus have been assumed to contribute to chromosome duplication in XRCC3 deficient colon cancer cells. This possibility was examined in other human cells. Chromosome duplication due to XRCC3 dysfunction was observed in cancer cells in which Cdt1 is stabilized, whereas it is not obviously observed in normal cells, in which Cdt1 is not stable. Because we previously showed that RPA is associated with XRCC3, the effect of RPA was examined in this system by RNA interference. Reduced levels of EPA prevented chromosome duplication induced by XRCC3 dysfunction, suggesting that EPA mediates the control of chromosome ploidy by XRCC3 in response to spontaneously arising DNA damage.

重要的是要了解细胞表型，响应自发产生的DNA损伤，而没有外源性DNA损伤。我们已经从染色体不稳定性的角度研究了同源重组功能改变对细胞功能的影响。因为Rad51B和XRCC3在与Rad51一致的同源重组中起作用，我们使用了这些基因被敲除的人结肠癌细胞系。我们已经证明Rad51B通过稳定中心体来防止非整倍体的产生。我们之前已经证明XRCC3可以防止染色体复制。Cdt1稳定性增加和Cdc6在细胞核中积累增加被认为有助于XRCC3缺陷结肠癌细胞中的染色体复制。这种可能性在其他人类细胞中进行了研究。在Cdt1稳定的癌细胞中观察到由于XRCC3功能障碍引起的染色体复制，而在Cdt1不稳定的正常细胞中未明显观察到。因为我们先前表明RPA与XRCC3相关，所以通过RNA干扰在该系统中检查RPA的作用。EPA水平的降低阻止了XRCC3功能障碍诱导的染色体复制，表明EPA介导了XRCC3对染色体倍性的控制，以响应自发产生的DNA损伤。

项目成果

The meiosis-specific synaptonemal compIex protein SCP3 is expressed in cancer and induces aneuploidy in somatic cells

减数分裂特异性联会复合体蛋白 SCP3 在癌症中表达并诱导体细胞非整倍性

• 发表时间: 2007
• 作者: Miyagawa K;Igaki H;Enomoto A;Igaki H;Miyagawa K;Igaki H;Enomoto A;Sasano N;Ikura T;Lee Motoyama JP;Suzuki T;Sasano N;Suzuki T;Lee Motoyama JP;Suzuki T;Nakai-Murakaimi C;Sarai N;Hosoi Y;Tonotsuka N;Date O;Miyagawa K;Miyagawa K;Miyagawa K;Miyagawa K;Miyagawa K;Katsura M;Tomoda Y;Katsura M;Tomoda Y;Katsura M;Tomoda Y;Hosoya N;Hosoya N;Hosoya N
• 通讯作者: Hosoya N

Human Rad54B associates with Werner syndrome protein WRN.

人类 Rad54B 与维尔纳综合征蛋白 WRN 相关。

• 发表时间: 2007
• 作者: Miyagawa K;Igaki H;Enomoto A;Igaki H;Miyagawa K;Igaki H;Enomoto A;Sasano N;Ikura T;Lee Motoyama JP;Suzuki T;Sasano N;Suzuki T;Lee Motoyama JP;Suzuki T;Nakai-Murakaimi C;Sarai N;Hosoi Y;Tonotsuka N;Date O;Miyagawa K;Miyagawa K;Miyagawa K;Miyagawa K;Miyagawa K;Katsura M;Tomoda Y
• 通讯作者: Tomoda Y

The meiosis-specific synaptonemal complex protein SCP3 is expressed in cancer and induces aneuploidy in somatic cells

减数分裂特异性联会复合体蛋白 SCP3 在癌症中表达并诱导体细胞非整倍性

• 发表时间: 2007
• 作者: Miyagawa K;Igaki H;Enomoto A;Igaki H;Miyagawa K;Igaki H;Enomoto A;Sasano N;Ikura T;Lee Motoyama JP;Suzuki T;Sasano N;Suzuki T;Lee Motoyama JP;Suzuki T;Nakai-Murakaimi C;Sarai N;Hosoi Y;Tonotsuka N;Date O;Miyagawa K;Miyagawa K;Miyagawa K;Miyagawa K;Miyagawa K;Katsura M;Tomoda Y;Katsura M;Tomoda Y;Katsura M;Tomoda Y;Hosoya N;Hosoya N
• 通讯作者: Hosoya N

Free Radical Scavenger Edaravone Suppresses X-ray-induced Apoptosis through p53 Inhibition in MOLT-4 Cells

自由基清除剂依达拉奉通过抑制 MOLT-4 细胞中的 p53 来抑制 X 射线诱导的细胞凋亡

• 发表时间: 2007
• 期刊: J Radiat Res (Tokyo) 48(6)
• 作者: Sasano N;Enomoto A;Hosoi Y;Katsumura Y;Matsumoto Y;Shiraishi K;Miyagawa K;Igaki H;Nakagawa K.
• 通讯作者: Nakagawa K.

Functional interaction between the transcription factor Kruppel-like facter 5 and popy (ADP-ribose) polymerase-1 in cardiovascular apoptosis

转录因子 Kruppel 样因子 5 和罂粟 (ADP-核糖) 聚合酶 1 在心血管细胞凋亡中的功能相互作用

• 发表时间: 2007
• 期刊: J Biol Chem 282
• 作者: K.Matsubara;et al.;Ikura T;Lee Motoyama JP;S.Muto and M.Horikoshi;Suzuki T
• 通讯作者: Suzuki T