Initiating DNA synthesis: from recruiting to activating the MCM complex

Lei, Ming; Tye, Bik K.

doi:10.1242/jcs.114.8.1447

Cited by 365DNA Repair MechanismsGenomics and Chromatin DynamicsCancer-related Molecular Pathways

Initiating DNA synthesis: from recruiting to activating the MCM complex

Lei, Ming, Tye, Bik K.·2001·Journal of Cell Science

DOI 10.1242/jcs.114.8.1447

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Abstract

The exact duplication of a genome once per cell division is required of every proliferating cell. To achieve this goal, eukaryotes adopt a strategy that limits every replication origin to a single initiation event within a narrow window of the cell cycle by temporally separating the assembly of the pre-replication complex (pre-RC) from the initiation of DNA synthesis. A key component of the pre-RC is the hexameric MCM complex, which is also the presumed helicase of the growing forks. An elaborate mechanism recruits the MCM complex to replication origins, and a regulatory chain reaction converts the poised, but inactive, MCM complex into an enzymatically active helicase. A growing list of proteins, including Mcm10 and Cdt1, are involved in the recruitment process. Two protein kinases, the Cdc7-Dbf4 kinase (DDK) and the cyclin-dependent kinase (CDK), trigger a chain reaction that results in the phosphorylation of the MCM complex and finally in the initiation of DNA synthesis. A composite picture from recent studies suggests that DDK is recruited to the pre-RC during G1 phase but must wait until S phase to phosphorylate the MCM complex. CDK is required for the recruitment of Cdc45 and other downstream components of the elongation machinery.

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Authors: Lei, M., & Tye, B. K.
Affiliations: Medical College of Wisconsin (US)
ORCID: Tye, Bik K.
Venue: Journal of Cell Science
Publisher: The Company of Biologists
Published: 2001-04-15
Volume: 114
Issue: 8
Pages: 1447-1454
ISSN: 0021-9533 (ISSN-L)
1477-9137
DOI: 10.1242/jcs.114.8.1447
OpenAlex: W1925747673
Cited by: 365
References: 105
Citations by year: 2025: 3 · 2024: 6 · 2023: 9 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 8 · 2017: 12 · 2016: 7 · 2015: 13 · 2014: 14 · 2013: 16 · 2012: 10
FWCI: 2.92
Type: journal article
Language: en
Open access: closed
Licence: www.biologists.com/user-licence-1-1/ (vor)
Locations: Journal of Cell Science (publishedVersion)
PubMed (publishedVersion)
Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: National Institutes of Health (5r01gm034190-22)
National Institute of General Medical Sciences (GM-34190)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: DNA replication initiation, MCM helicase, pre-replication complex, origin of replication, cyclin-dependent kinases, MCM10, Cdt1, Cdc45, replication fork, G1/S transition
MeSH terms: Animals, Carrier Proteins, Chromatin, Chromosomal Proteins, Non-Histone, DNA, DNA Replication, DNA Helicases, DNA-Binding Proteins, Humans, Nuclear Proteins, Saccharomyces cerevisiae, Cell Cycle Proteins, Cyclin-Dependent Kinases, Saccharomyces cerevisiae Proteins, Origin Recognition Complex, Minichromosome Maintenance Proteins, Minichromosome Maintenance Complex Component 7

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Initiating DNA synthesis: from recruiting to activating the MCM complex

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