中文摘要
同源重组是体内DNA双链断裂的主要修复途径,也是有性生殖中减数分裂的必要环节,在维持基因组完整性和稳定性方面发挥着关键的作用。同源重组在DNA水平上的分子进程研究得比较深入,然而在染色质水平上调控机制的探索目前相对较少。组蛋白分子伴侣结合组蛋白,介导核小体内组蛋白-DNA间的相互作用,是重要的表观遗传调控蛋白。本人长期从事植物组蛋白分子伴侣的分子与功能研究,所在团队近期首次报道了特异性结合组蛋白H2A-H2B的分子伴侣NAP1和NRP蛋白参与调控植物体细胞同源重组。然而,NAP1和NRP如何调控同源重组,以及为何仅特异性调控体细胞同源重组,其分子机理目前并不清楚。我们旨在通过本项目的资助,研究同源重组过程中NAP1和NRP在组蛋白(变体)调控、相关基因转录调控以及蛋白互作等方面的功能与作用,解析核小体结构调节与同源重组发生的功能关联,探索在染色质水平上调控同源重组的表观遗传机制。
英文摘要
Homologous recombination (HR) is a major pathway in repairing DNA double strand breaks in vivo, and also the critical step during meiosis in sexual reproduction, thus playing crucial roles in the maintenance of genome stability and integrity. Compared to the well-studied molecular progression of HR at the DNA level, the regulatory mechanism of HR at the chromatin level is less understood. Histone chaperones bind histones, and function as important epigenetic regulatory proteins by mediating histone-DNA interaction within nucleosomes. I, the applicant, work on the molecular and functional characterization of plant histone chaperones. Recently, our team first reported the functional implication of histone chaperones NAP1 and NRP, both of which are specific to histone H2A-H2B, in the regulation of plant somatic HR. However, the underlying molecular mechanism(s) of NAP1 and NRP in HR progression, as well as their specificity in somatic HR, are still not clear. We plan to investigate the involvement of NAP1 and NRP in histone (variant) dynamics, transcriptional regulation of HR-related genes, and protein-protein interactions and their functional crosstalk in HR. We try to find the functional connection of nucleosome dynamics and HR progression, and to unravel the epigenetic mechanism(s) underlying the regulation on HR frequency at the chromatin level under the support of this grant.
