植物DNA损伤应答途径中γ-H2A.X阅读蛋白的功能研究

双链DNA断裂（DSB）发生后，邻近的组蛋白变体H2A.X被迅速磷酸化为γ-H2A.X，成为触发后续DSB信号传导和修复途径的关键信号。尽管在酵母和动物中与γ-H2A.X相关的DNA损伤反应（DDR）已经得到深入的研究，但是目前植物的γ-H2A.X阅读蛋白仍然未被发现，导致植物DDR中的相应途径仍然不清楚。申请人筛选出特异性结合γ-H2A.X的拟南芥阅读蛋白，命名为XIP（γ-H2A.X-interacting protein）。本项目旨在利用生物化学、遗传学、结构生物学、生物信息学等多种研究手段，深入研究该阅读蛋白的分子功能，通过解析XIP识别γ-H2A.X的结构基础，寻找XIP调控的靶基因，从而阐明XIP这一植物特有的蛋白在植物DSB修复途径中的生物学功能。本项目的研究对揭示XIP在DSB修复途径中的分子机制及完善DDR通路相关遗传调控网络具有重要意义。

Upon the occurrence of DNA double strand break (DSB), proximal histone variant H2A.X is quickly phosphorylated as γ-H2A.X, which emerges as a critical signal in triggering following DSB signaling and repair pathway. Although γ-H2A.X-linked DNA damage response (DDR) has been well-characterized in yeast and animals, the corresponding reader of plant γ-H2A.X has not been identified yet, and the corresponding pathway in plant DDR remains obscure. We have screened out one Arabidopsis protein specifically interacting with γ-H2A.X and designated it as XIP (γ-H2A.X-Interacting Protein). This project aims to characterize the molecular function of this plant-specific reader protein by biochemical, genetic, bioinformatic and other research approaches. I plan to unravel the structural basis for the recognition of XIP to γ-H2A.X, survey the target genes of XIP, and clarify the biological role of plant-specific XIP in the DSB repair pathway. Revealing the molecular mechanism of XIP in DSB repair pathway will improve our knowledge of the complicated regulatory network related to the DDR pathway.