香港大学翟元梁研究组发现，人类的预复制复合物是一个开放的复合物。相关论文于2023年1月5日发表在《细胞》杂志上。

Title: The human pre-replication complex is an open complex

Author: Jian Li, Jiangqing Dong, Weitao Wang, Daqi Yu, Xinyu Fan, Yan Chit Hui, Clare S.K. Lee, Wai Hei Lam, Nathan Alary, Yang Yang, Yingyi Zhang, Qian Zhao, Chun-Long Chen, Bik-Kwoon Tye, Shangyu Dang, Yuanliang Zhai

Issue&Volume: 2023/01/05

Abstract: In eukaryotes, DNA replication initiation requires assembly and activation of theminichromosome maintenance (MCM) 2–7 double hexamer (DH) to melt origin DNA strands.However, the mechanism for this initial melting is unknown. Here, we report a 2.59-cryo-electron microscopy structure of the human MCM-DH (hMCM-DH), also known as thepre-replication complex. In this structure, the hMCM-DH with a constricted centralchannel untwists and stretches the DNA strands such that almost a half turn of thebound duplex DNA is distorted with 1 base pair completely separated, generating aninitial open structure (IOS) at the hexamer junction. Disturbing the IOS inhibitsDH formation and replication initiation. Mapping of hMCM-DH footprints indicates thatIOSs are distributed across the genome in large clusters aligning well with initiationzones designed for stochastic origin firing. This work unravels an intrinsic mechanismthat couples DH formation with initial DNA melting to license replication initiationin human cells.

DOI: 10.1016/j.cell.2022.12.008

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01521-5