聚ADP核糖化（PAR化）是细胞内重要的蛋白质翻译后修饰方式，主要由PARP1介导。PARP1的活化会产生游离的Free PAR，现已发现Free PAR能够参与细胞的多种重要生物学事件，如细胞凋亡、染色质改构、RNA剪接等。但是Free PAR在基因表达调控中的作用，相关机制尚待阐明。ARE元件及ARE结合蛋白是影响mRNA稳定性的重要调节因素之一。我们在前期的实验中发现，Free PAR能够与ARE结合蛋白HuB非共价结合，并促进HuB结合靶mRNA的作用。本项目将在已有研究的基础上，深入探讨：1）细胞应答DNA损伤刺激时，Free PAR与HuB相互作用是否参与基因表达调控；2）Free PAR与HuB相互作用的分子机制；3）Free PAR与HuB相互作用对于细胞损伤应答的生理意义。本项目的完成将揭示Free PAR在转录后水平调节基因表达的新机制及参与细胞损伤应答的新功能。

Poly(ADP-ribosyl)ation is one of the essential posttranslational modification of proteins, catalyzed by PARP family proteins, and of which, PARP1 is the most important member. Covalently attached PAR can be hydrolyzed to Free PAR if PARP1 over activity. PAR binds with proteins in noncovalent manner has been reported participated in a variety of biological process,such as cell death, chromatin remodeling, RNA splicing. However, Free PAR's role in regulation of gene expression needs further explorer. AU-rich element (ARE) and ARE-binding proteins are major mRNA stabilization determinants.Our on-going study showed, Free PAR non-covalent bind with ARE binding protein HuB and increase its binding with mRNA. Based on the obtained results, this study will mainly focused on: 1) In the condition of cellular DNA damage response, whether Free PAR together with HuB involved in regulating gene expression; 2) what is the molecular mechanisms of interaction between Free PAR and HuB; 3) revealing the significant of Free PAR interacts with HuB in cell damage response. We anticipate that our data from these studies will reveal the new features of Free PAR involved in regulation of gene expression and cellular damage response.