MOLECULAR FUNCTION OF DNA REPAIR FOR THE DEVELOPMENT

DNA 修复的分子功能促进发育

• 批准号: 15390323
• 负责人: MIZUTANI Shuki
• 金额: $ 9.47万
• 依托单位: TOKYO MEDICAL AND DENTAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390323/
• 关键词: DNA STRAND BREAKS; ATM; MLL; G2; M; ARTEMIS; DNA-PK; MRN complex; 乳児白血病; TopoIIインヒビター

ATM is a gene involved in the pathogenesis of Ataxia Telangiectasia and plays an important role in genome surveillance system. We found ATM mutation allow cells to override G2/M checkpoint in response to topoisomerase II (Topo II) inhibitor. Topo II inhibitor also cleaves MLL gene. These finding led us to investigate possible MLL translocation by Topo II inhibitor in ATM deficient cells. As the result we demonstrated frequent MLL translocation in these conditions by FISH analyses.Artemis is a molecule involved in the development of primary immune deficiency and phosphorylated by DNA-PKcs. We found ATM is phosphorylated at S645 in ATM dependent manner in response to XIR. These findings placed Artemtis at the crossing road between ATM and DNA-Pkcs.

ATM是参与共济失调毛细血管扩张症发病的基因，在基因组监测系统中起重要作用。我们发现ATM突变允许细胞响应拓扑异构酶II（Topo II）抑制剂而越过G2/M检查点。Topo II抑制剂也切割MLL基因。这些发现使我们研究ATM缺陷细胞中Topo II抑制剂可能的MLL易位。结果表明，在这些条件下，我们通过FISH分析证实了频繁的MLL易位。Artemis是一种参与原发性免疫缺陷发展的分子，并被DNA-PKcs磷酸化。我们发现ATM在S645以ATM依赖的方式被磷酸化，以响应XIR。这些发现将Artemtis置于ATM和DNA-Pkcs之间的交叉路口。

项目成果

Allogeneic hematopoietic stem cell transplantation for seven children with X‐linked hyper‐IgM syndrome: A single center experience

• DOI: 10.1002/ajh.20044
• 发表时间: 2004-05
• 期刊: American Journal of Hematology
• 影响因子: 12.8
• 作者: D. Tomizawa;K. Imai;Sukeyuki Ito;M. Kajiwara;Y. Minegishi;M. Nagasawa;T. Morio;S. Nonoyama;S. Mizutani

Nagasawa M, Mizutani S., et al.: "Coagulopathy in a patient with X-linked hyper-IgM syndrome who developed Kaposi's sarcoma."Am J Hematol.. 75. 116-117 (2004)

Nagasawa M, Mizutani S., et al.：“患有 X 连锁高 IgM 综合征并发展为卡波西肉瘤的患者的凝血病。”Am J Hematol.. 75. 116-117 (2004)

Coordinated regulation of the promoter and enhancer regions of human CD23 gene by signal through IL-4R and CD40, and the role of Ku70/80 in the enhancer activity.

• DOI: 10.11480/jmds.500203
• 发表时间: 2003-06
• 期刊: Journal of medical and dental sciences
• 作者: M. Imai;S. Mizutani;T. Morio

DNA damage-induced cell-cycle phase regulation of p53 and p21waf1 in normal and ATM-defective cells

• DOI: 10.1038/sj.onc.1207086
• 发表时间: 2003-10-30
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Delia, D;Fontanella, E;Mizutani, S
• 通讯作者: Mizutani, S

Clinical course of patients with WASP gene mutations

• DOI: 10.1182/blood-2003-05-1480
• 发表时间: 2004-01-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Imai, K;Morio, T;Nonoyama, S
• 通讯作者: Nonoyama, S