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衰老与DNA双链断裂损伤修复

衰老与DNA双链断裂损伤修复
  • 导航:首页 > 科学基金
  • 批准号:81622019
  • 批准年度: 2016年
  • 学科分类:老年医学(H2501) |
  • 项目负责人:毛志勇
  • 负责人职称:教授
  • 依托单位:同济大学
  • 资助金额:130万元
  • 项目类别:优秀青年科学基金项目
  • 研究期限:2017年01月01日 至 2019年12月31日
  • 中文关键词: 衰老;DNA;双链;断裂;损伤
  • 英文关键词:mechanisims of aging;genomic stability;DNA double strand break repair;nonhomologous end joining;homo

项目摘要

中文摘要

申请人毛志勇博士自2012年9月担任同济大学附属第一妇婴保健院教授,主要从事衰老相关的DNA双链断裂修复调控机制的研究和教学工作。申请人主要学术贡献归纳为三点:揭示衰老可导致基因组稳定性下调的现象,阐述衰老相关蛋白调控DNA损伤修复的分子机制,为发展延缓衰老的方法提供理论基础;揭示了相较正常细胞,肿瘤细胞同源重组修复通路被显著激活这一现象,并阐述了同源重组修复提升的可能机制,最终基于此现象发展特异性的靶向肿瘤载体;阐述了不同细胞周期时DNA双链断裂修复通路选择以及修复的动力学,为深入探索两条修复通路选择奠定了初步基础。申请人以通讯作者或共同通讯作者在Oncotarget、MCB、Cell Cycle以及Plos One发表4篇文章,以第一作者在Science、PNAS等杂志发表7篇文章,以共同作者在Nature、PNAS等杂志发表10篇文章。

英文摘要

Dr. Zhiyong Mao joined the Shanghai First Maternity & Infant Hospital, Tongji University as a professor since September, 2012. He has been focusing himself on elucidating molecular mechanisms of age-associated DNA repair for over 10 years. Using reporter cassettes for quantitatively and rapidly analyzing the repair efficiency of nonhomologous end joining (NHEJ) and homologous recombination (HR)– two repair pathways responsible for fixing DNA double strand (DSB) breaks, Dr. Mao has addressed several important questions in the fields of aging related DNA repair. His major contribution includes: (1). He uncovered the molecular mechanisms of regulating DNA DSB repair by SIRT6, a protein involved in aging. His findings laid the foundation of developing small molecules activating SIRT6 for delaying aging and curing cancer; (2). He found that in comparison to that in normal HMEC cells, HR efficiency in breast cancer cells was significantly increased. Further mechanistic studies indicate that the interplay between Rad6 and HP1 might play a role in the elevation of HR. Based on this, he developed a tool for cancer therapy with Rad51C promoter for transcriptional targeting of cancer cells; (3). Using the unique reporter cell lines for studying NHEJ and HR, he systematically studies several fundamental aspects of both pathways. He analyzed the usage of both pathways in primary cells with intact checkpoints. He also compared the repair kinetics of two pathways, and different utilization of two pathways in different cell cycle stages. Dr. Mao has published 21 papers, including 4 papers published in Oncotarget, MCB, Cell Cycle and Plos One as corresponding author or co-corresponding authors, 7 first authored papers published in Science, PNAS and etc., 10 papers published in Nature, PNAS and other journals as co-authors.

评估说明

    国家自然科学基金项目“衰老与DNA双链断裂损伤修复”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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