ArticlePLoS genetics2021
The capacity of origins to load MCM establishes replication timing patterns.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- OCT4 enhances the firing efficiency of late DNA replication origins in mouse embryonic stem cells.Nature communications · 2026Article
- Compact Origins and Where to Find Them: ORC's Guide to Genome-Wide Licensing.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Loss of G1-phase CDK-inhibition biases instability between genomic regions by unevenly reducing activity among replication origins.iScience · 2025Article
- MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing.Nature communications · 2024Article
- Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution.Nature communications · 2024Article
- Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.Molecular diagnosis & therapy · 2024Review
- Identification of 1600 replication origins ineLife · 2024Article
- Where and when to start: Regulating DNA replication origin activity in eukaryotic genomes.Nucleus (Austin, Tex.) · 2023Review
- Broadly Applicable Control Approaches Improve Accuracy of ChIP-Seq Data.International journal of molecular sciences · 2023Article
- Replication timing and transcriptional control: beyond cause and effect - part IV.Current opinion in genetics & development · 2023Review
- The conserved histone chaperone Spt6 is strongly required for DNA replication and genome stability.Cell reports · 2023Article
- Review
- DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Global early replication disrupts gene expression and chromatin conformation in a single cell cycle.Genome biology · 2022Article
- The consequences of differential origin licensing dynamics in distinct chromatin environments.Nucleic acids research · 2022Article
- Review
- Article
- Efficiency and equity in origin licensing to ensure complete DNA replication.Biochemical Society transactions · 2021Review
- Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Loading of the MCM replicative helicase at origins of replication is a highly regulated process that precedes DNA replication in all eukaryotes. The stoichiometry of MCM loaded at origins has been proposed to be a key determinant of when those origins initiate replication during S phase. Nevertheless, the genome-wide regulation of MCM loading stoichiometry and its direct effect on replication timing remain unclear. In order to investigate why some origins load more MCM than others, we perturbed MCM levels in budding yeast cells and, for the first time, directly measured MCM levels and replication timing in the same experiment. Reduction of MCM levels through degradation of Mcm4, one of the six obligate components of the MCM complex, slowed progression through S phase and increased sensitivity to replication stress. Reduction of MCM levels also led to differential loading at origins during G1, revealing origins that are sensitive to reductions in MCM and others that are not. Sensitive origins loaded less MCM under normal conditions and correlated with a weak ability to recruit the origin recognition complex (ORC). Moreover, reduction of MCM loading at specific origins of replication led to a delay in their replication during S phase. In contrast, overexpression of MCM had no effects on cell cycle progression, relative MCM levels at origins, or replication timing, suggesting that, under optimal growth conditions, cellular MCM levels are not limiting for MCM loading. Our results support a model in which the loading capacity of origins is the primary determinant of MCM stoichiometry in wild-type cells, but that stoichiometry is controlled by origins' ability to recruit ORC and compete for MCM when MCM becomes limiting.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.