Cryo-EM structure of human hexameric MCM2-7 complex

Xu，Naining1,2; Lin，Qingpeng3; Tian，Honglei2; Liu，Changdong2,4; Wang，Peiyi5; Suen，Ching Monica2; Yang，Hongyu1; Xiang，Ye3; Zhu，Guang2,4,6

2022-09-16

10.1016/j.isci.2022.104976

iScience   Impact Factor & Quartile

2589-0042

The central step in the initiation of eukaryotic DNA replication is the loading of the minichromosome maintenance 2–7 (MCM2-7) complex, the core of the replicative DNA helicase, onto chromatin at replication origin. Here, we reported the cryo-EM structure of endogenous human single hexameric MCM2-7 complex with a resolution at 4.4 Å, typically an open-ring hexamer with a gap between Mcm2 and Mcm5. Strikingly, further analysis revealed that human MCM2-7 can self-associate to form a loose double hexamer which potentially implies a novel mechanism underlying the MCM2-7 loading in eukaryote. The high-resolution cryo-EM structure of human MCM2-7 is critical for understanding the molecular mechanisms governing human DNA replication, especially the MCM2-7 chromatin loading and pre-replicative complex assembly.

Cell biology Molecular biology Structural biology

SCI

English

Others

Basic and Applied Basic Research Foundation of Guangdong Province[2020A1515010034];Basic and Applied Basic Research Foundation of Guangdong Province[2021A1515220104];Ministry of Science and Technology of the People's Republic of China[2021YFA1300204];National Natural Science Foundation of China[21827810];National Natural Science Foundation of China[31925023];National Natural Science Foundation of China[32071188];

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000860341500008

CELL PRESS

2-s2.0-85137647749

Scopus

1.Department of Oral and Maxillofacial Surgery,Stomatological Center,Peking University Shenzhen Hospital,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen,518036,China
2.Division of Life Science,The Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong SAR,00000,China
3.Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,Center for Infectious Disease Research,Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing,100084,China
4.HKUST Shenzhen Research Institute,Hi-Tech Park,Nanshan,Shenzhen,518057,China
5.Cryo-EM Center of SUSTech,Southern University of Science and Technology,Shenzhen,518055,China
6.State Key Laboratory of Molecular Neuroscience,The Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong SAR,00000,China

Xu，Naining,Lin，Qingpeng,Tian，Honglei,et al. Cryo-EM structure of human hexameric MCM2-7 complex[J]. iScience,2022,25(9).

Xu，Naining.,Lin，Qingpeng.,Tian，Honglei.,Liu，Changdong.,Wang，Peiyi.,...&Zhu，Guang.(2022).Cryo-EM structure of human hexameric MCM2-7 complex.iScience,25(9).

Xu，Naining,et al."Cryo-EM structure of human hexameric MCM2-7 complex".iScience 25.9(2022).