The human pre-replication complex is an open complex.

Autor:	Li J; School of Biological Sciences, The University of Hong Kong, Hong Kong, China., Dong J; Division of Life Science, Center of Systems Biological and Human Health, The Hong Kong University of Science and Technology, Hong Kong, China., Wang W; Institut Curie, PSL Research University, CNRS UMR3244, Dynamics of Genetic Information, Sorbonne Université, 75005 Paris, France., Yu D; Division of Life Science, Center of Systems Biological and Human Health, The Hong Kong University of Science and Technology, Hong Kong, China., Fan X; School of Biological Sciences, The University of Hong Kong, Hong Kong, China., Hui YC; School of Biological Sciences, The University of Hong Kong, Hong Kong, China., Lee CSK; School of Biological Sciences, The University of Hong Kong, Hong Kong, China., Lam WH; School of Biological Sciences, The University of Hong Kong, Hong Kong, China., Alary N; Institut Curie, PSL Research University, CNRS UMR3244, Dynamics of Genetic Information, Sorbonne Université, 75005 Paris, France., Yang Y; State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China., Zhang Y; Biological Cryo-EM Center, The Hong Kong University of Science and Technology, Hong Kong, China., Zhao Q; State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China., Chen CL; Institut Curie, PSL Research University, CNRS UMR3244, Dynamics of Genetic Information, Sorbonne Université, 75005 Paris, France. Electronic address: chunlong.chen@curie.fr., Tye BK; Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong, China; Department of Molecular Biology & Genetics, Cornell University, Ithaca, NY 14853, USA. Electronic address: biktye@ust.hk., Dang S; Division of Life Science, Center of Systems Biological and Human Health, The Hong Kong University of Science and Technology, Hong Kong, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China; HKUST-Shenzhen Research Institute, Nanshan, Shenzhen 518057, China. Electronic address: sdang@ust.hk., Zhai Y; School of Biological Sciences, The University of Hong Kong, Hong Kong, China. Electronic address: zhai@hku.hk.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2023 Jan 05; Vol. 186 (1), pp. 98-111.e21.
DOI:	10.1016/j.cell.2022.12.008
Abstrakt:	In eukaryotes, DNA replication initiation requires assembly and activation of the minichromosome 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-Å cryo-electron microscopy structure of the human MCM-DH (hMCM-DH), also known as the pre-replication complex. In this structure, the hMCM-DH with a constricted central channel untwists and stretches the DNA strands such that almost a half turn of the bound duplex DNA is distorted with 1 base pair completely separated, generating an initial open structure (IOS) at the hexamer junction. Disturbing the IOS inhibits DH formation and replication initiation. Mapping of hMCM-DH footprints indicates that IOSs are distributed across the genome in large clusters aligning well with initiation zones designed for stochastic origin firing. This work unravels an intrinsic mechanism that couples DH formation with initial DNA melting to license replication initiation in human cells. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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