SND1蛋白参与调控DNA损伤应答分子机制的研究

项目名称： SND1蛋白参与调控DNA损伤应答分子机制的研究

项目编号： No.31501056

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 付晓

作者单位： 天津医科大学

项目金额： 20万元

中文摘要： SND1蛋白是一种广泛存在的多功能蛋白，参于基因转录、pre-mRNA剪接、脂代谢以及细胞应激、细胞周期等过程。本课题组一直从事相关研究，最新发现敲除SND1蛋白会加剧DNA损伤和诱发细胞凋亡。我们通过质谱分析并验证了SND1蛋白可以和PARP-1蛋白相互结合，同时检测到SND1蛋白可以发生多聚ADP核糖基化修饰。PARP-1蛋白主要参与DNA损伤的识别和修复。此外我们还发现SND1蛋白的敲除导致H3K9ac和ATM通路磷酸化的差异表达。本项目旨在研究SND1蛋白对DNA损伤和细胞凋亡的影响；SND1蛋白被PARP-1蛋白调控以及在DNA损伤位点的募集；SND1蛋白通过影响表观遗传调控松弛染色质结构，促进ATM磷酸化通路的激活，深入探讨其参与调控DNA损伤应答的分子机制，有助于揭示SND1蛋白在衰老、哮喘、肿瘤等多种临床相关疾病的作用机理。

中文关键词： 人类；表观遗传调控；差异表达；DNA损伤应答；SND1蛋白

英文摘要： SND1 protein is a highly conserved and ubiquitously expressed multifunctional protein. It implicated in a variety of cellular processes, such as gene transcription, pre-mRNA splicing, adipogenesis, as well as formation of stress granules and cell cycle. It is important to note that SND1 knockout aggravates DNA damage and induces apoptosis. The data of mass spectrometry indicated that SND1 could bind with PARP-1 and become modified by Poly(ADP-ribosyl)ation. PARP-1 is involved in DNA-break sensing and signaling in the cellular response to DNA damage. In addition, SND1 knockout induced differential expressions of H3K9ac and phosphorylation of ATM protein kinase. Our main purpose of this study is to explore: SND1 is associated with DNA damage and apoptosis; PARP1 regulates SND1 recruitment to sites of DNA damage; SND1 is required for chromatin relaxation via epigenetic regulation upon DNA damage and activates ATM-dependent DNA damage signaling pathway. Here, we discuss the potential role of SND1 in DNA damage response and its possible function mechanism to exploit its role in aging, inflammation and cancer.

英文关键词： human;epigenetic regulation;differential expression;DNA damage response; SND1 protein