Unique Roles of the Non-identical MCM Subunits in DNA Replication Licensing

Yuanliang Zhai; Ningning Li; Hanlun Jiang; Xuhui Huang; Ning Gao; Bik Kwoon Tye

doi:10.1016/j.molcel.2017.06.016

Unique Roles of the Non-identical MCM Subunits in DNA Replication Licensing

Mol Cell. 2017 Jul 20;67(2):168-179. doi: 10.1016/j.molcel.2017.06.016.

Authors

Yuanliang Zhai¹, Ningning Li², Hanlun Jiang³, Xuhui Huang³, Ning Gao⁴, Bik Kwoon Tye⁵

Affiliations

¹ Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: [email protected].
² State Key Laboratory of Membrane Biology, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China.
³ Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
⁴ State Key Laboratory of Membrane Biology, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China; Ministry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China. Electronic address: [email protected].
⁵ Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Department of Molecular Biology and Genetics, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY, USA. Electronic address: [email protected].

PMID: 28732205
DOI: 10.1016/j.molcel.2017.06.016

Abstract

A family of six homologous subunits, Mcm2, -3, -4, -5, -6, and -7, each with its own unique features, forms the catalytic core of the eukaryotic replicative helicase. The necessity of six similar but non-identical subunits has been a mystery since its initial discovery. Recent cryo-EM structures of the Mcm2-7 (MCM) double hexamer, its precursors, and the origin recognition complex (ORC)-Cdc6-Cdt1-Mcm2-7 (OCCM) intermediate showed that each of these subunits plays a distinct role in orchestrating the assembly of the pre-replication complex (pre-RC) by ORC-Cdc6 and Cdt1.

Keywords: Acrobat Model for pre-RC assembly; DNA replication initiation; Mcm2–7; ORC-Cdc6-Cdt1-MCM; cryo-EM structures.

Publication types

Review

MeSH terms

Animals
Catalytic Domain
Cell Cycle Proteins / metabolism
DNA Replication*
Humans
Minichromosome Maintenance Proteins / chemistry
Minichromosome Maintenance Proteins / metabolism*
Minichromosome Maintenance Proteins / ultrastructure
Models, Molecular
Multiprotein Complexes
Nuclear Proteins / metabolism
Nucleic Acid Conformation
Origin Recognition Complex / chemistry
Origin Recognition Complex / metabolism*
Origin Recognition Complex / ultrastructure
Protein Binding
Protein Subunits
Structure-Activity Relationship

Substances

CDC6 protein, human
CDT1 protein, human
Cell Cycle Proteins
Multiprotein Complexes
Nuclear Proteins
Origin Recognition Complex
Protein Subunits
Minichromosome Maintenance Proteins