报告题目：Chromatin based DNA replication regulation
报告人：龙海珍 深圳湾实验室特聘研究员
报告地点：99905银河官方网生命科学楼408会议室
报告时间：2023年10月10日下午1:30
主办单位：99905银河官方网
报告人简介：
龙海珍，深圳湾实验室分子生理所特聘研究员。本科毕业于湖南师范大学，博士毕业于中国科学院生物物理研究所。深圳市优秀青年基金、中国科协“青年人才托举工程”项目获得者。以第一、共同第一或共同通讯作者身份在Nature、Molecular Cell、 Nature Structural & Molecular Biology、 BMC Biology等国际权威学术期刊上发表论文。研究成果荣获2020年度中国科学十大进展（进展四：揭示人类遗传物质传递的关键步骤），以及国家“十三五”科技创新成就展。课题组的研究方向为DNA复制的表观遗传调控机制及其在肿瘤发生发展和细胞分化发育过程的作用。
报告摘要：
DNA replication is a tightly regulated process that ensures the precise duplication of the genome during the cell cycle. In eukaryotes, the licensing and activation of replication origins are regulated by both DNA sequence and chromatin features. However, the chromatin-based regulatory mechanisms remain largely uncharacterized. Here, we show that the histone variant H2A.Z, which binds the enzyme SUV420H1 to promote the dimethylation of histone H4, which in turn recruits the origin recognition complex subunit 1(ORC1). Our results suggest that the histone variant H2A.Z epigenetically regulates the licensing and activation of early replication origins and maintains replication timing through the SUV420H1–H4K20me2–ORC1 axis. To further investigate the mechanism by which SUV420H1 preferentially recognizes H2A.Z-nucleosome and deposits H4 lysine 20 dimethylation (H4K20me2) on DNA replication origins, we determined the cryo-EM structures of SUV420H1 bound to H2A.Z-nucleosome or H2A-nucleosome. Collectively, our findings elucidate how SUV420H1 preferentially recognizes H2A.Z-nucleosome to deposit H4K20me2 modification and shed light on therapeutic strategies targeting the DNA replication initiation.
