Analysis of meiotic DNAdamage checkpoint

减数分裂 DNA 损伤检查点分析

• 批准号: 14370518
• 负责人: HAYASHI Yutaro
• 金额: $ 3.01万
• 依托单位: NAGOYA CITY UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370518/
• 关键词: meiosis; DNA damaae checkpoint; fission yeast; 細胞周期

Molecular mechanism in human meiosis is still unknown as no effective methods are established to analyze. We examined checkpoint system to DNA damage during fission yeast meiosis.In vegetative cdsl cells, checkpoint Rad (Rad1, Rad3 etc.) dependent activation of Chk1 in response to hydroxyurea(HU) arrest the cell cycle in G2. But Chk1 dependent response to HU during meiosis is attenuated. To investigate the existence of meiotic DNA damage checkpoint system, rad1, chk1, cds1 mutants are treated with alkylating agent methylmethane sulfonate(MMS; 0.01%) during early meiosis. These mutants undergo aberrant chromosomal segregation, delayed and abnormal meiotic divisions at s similar rate to wild type. In meiotic cds1 cells with MMS, subtle phosphorylation in Chk1 protein is observed in immunoblot, compared to the vegetative cells. Cdc2-Tyr15 in meiotic S phase is also dephosphorylated. The DNA damage response of checkpoint mutants to MMS in this study suggests DNA damage checkpoint in fission yeast meiosis is attenuated or not in existence.Recently, other groups have demonstrated that spontaneous S phase damage is repaired by activating recombination without checkpoint arrest. It is not shown whether the checkpoint aberration causes meiotic abnormality in human. As some genes related to the DNA recombination have already identified in human, it would be significant to examine the genes to know the molecular mechanism in meiosis.

由于没有建立有效的分析方法，人类减数分裂的分子机制仍然是未知的。我们研究了裂殖酵母减数分裂过程中DNA损伤的检查点系统，在营养细胞中，检查点Rad（Rad 1，Rad 3等）响应于羟基脲（HU）的Chk 1的依赖性活化将细胞周期阻滞在G2。但在减数分裂过程中，Chk 1依赖的对HU的反应减弱。为了研究减数分裂DNA损伤检查点系统的存在，在减数分裂早期用烷化剂甲基甲烷磺酸盐（MMS; 0.01%）处理rad 1，chk 1，cds 1突变体。这些突变体以与野生型相似的速率经历异常的染色体分离、延迟和异常的减数分裂。与营养细胞相比，在具有MMS的减数分裂cds 1细胞中，在免疫印迹中观察到Chk 1蛋白的细微磷酸化。Cdc 2-Tyr 15在减数分裂S期也被脱磷酸化。本研究中检测点突变体对MMS的DNA损伤反应表明裂殖酵母减数分裂中的DNA损伤检测点被减弱或不存在。最近，其他研究小组已经证明自发的S期损伤是通过激活重组而修复的，而没有检测点停滞。尚未显示检查点畸变是否导致人类减数分裂异常。在人类中已经发现了一些与DNA重组相关的基因，因此研究这些基因对了解减数分裂的分子机制具有重要意义。

项目成果

Molecular mechanism of DNA replication and damage checkpoint

DNA复制和损伤检查点的分子机制

• 发表时间: 2005
• 期刊: JIKKEN IGAKU 23
• 作者: Hiroshi Murakami

分裂酵母・出芽酵母における減数分裂の細胞周期制御機構

裂殖酵母和芽殖酵母减数分裂细胞周期控制机制

• 发表时间: 2002
• 期刊: 実験医学 20
• 作者: Ito K;Fujita T;Akada M;Kiniwa Y;Tsukamoto M;Yamamoto A;Matsuzaki Y;Matsushita M;Asano T;Nakashima J;Tachibana M;Hayakawa M;Ikeda H;Murai M;Kawakami Y.;渡並 優子
• 通讯作者: 渡並 優子

Scrotal dartos flap for the prevention of the urethrocutaneous fistula on hypospadias urethroplasty

• DOI: 10.1111/j.1442-2042.2005.01028.x
• 发表时间: 2005-03-01
• 期刊: INTERNATIONAL JOURNAL OF UROLOGY
• 影响因子: 2.6
• 作者: Hayashi, Y;Kojima, Y;Kohri, K
• 通讯作者: Kohri, K

DNA複製と損傷チェックポイントの分子機構

DNA复制和损伤检查点的分子机制

• 发表时间: 2005
• 期刊: 実験医学増刊号 23
• 作者: 村上 浩士

Novel technique for correcting penile curvature with severe hypospadias ; ventral lengthening with tunica vaginalis flap patching

矫正严重尿道下裂阴茎弯曲的新技术；

• 发表时间: 2005
• 期刊: Int J Urol. 12
• 作者: Roy BC;Aoyagi T;Sarkar S;Nomura K;Kanda H;Iwaya K;Tachibana M;Koyama R.;Yutaro Hayashi
• 通讯作者: Yutaro Hayashi