ArticlePloS one2011
Cdc45 limits replicon usage from a low density of preRCs in mammalian cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 97 citations in OpenAlex.
- Outside-in progression of heterochromatin replication and exclusion of CDC45 from the PCH domain inbioRxiv : the preprint server for biology · 2026Article
- Autosomal dominant CDC45 deficiency with allelic expression bias causes a novel genetic disease of the immune system.bioRxiv : the preprint server for biology · 2026Article
- Cell cycle-dependent TICRR/TRESLIN and MTBP chromatin binding mechanisms and patterns.Genome biology · 2025Article
- Polymerase-usage sequencing identifies initiation zones with less bias across S phase in mouse embryonic stem cells.Journal of biochemistry · 2025Article
- HROB Is Implicated in DNA Replication.Genes · 2024Article
- Identification of ATP-Competitive Human CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function.Molecular cancer therapeutics · 2024Article
- Quantity and quality of minichromosome maintenance protein complexes couple replication licensing to genome integrity.Communications biology · 2024Review
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
- Neural network and kinetic modelling of human genome replication reveal replication origin locations and strengths.PLoS computational biology · 2023Article
- Review
- DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- LSD1 is required for euchromatic origin firing and replication timing.Signal transduction and targeted therapy · 2022Article
- The CRL4DTL E3 ligase induces degradation of the DNA replication initiation factor TICRR/TRESLIN specifically during S phase.Nucleic acids research · 2021Article
- LRR1-mediated replisome disassembly promotes DNA replication by recycling replisome components.The Journal of cell biology · 2021Article
- Reduced replication origin licensing selectively kills KRAS-mutant colorectal cancer cells via mitotic catastrophe.Cell death & disease · 2020Article
- Myc and the Replicative CMG Helicase: The Creation and Destruction of Cancer: Myc Over-Activation of CMG Helicases Drives Tumorigenesis and Creates a Vulnerability in CMGs for Therapeutic Intervention.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Review
- Genomic methods for measuring DNA replication dynamics.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2020Review
- Origin Recognition Complex (ORC) Evolution Is Influenced by Global Gene Duplication/Loss Patterns in Eukaryotic Genomes.Genome biology and evolution · 2020Article
- Review
- Preparation for DNA replication: the key to a successful S phase.FEBS letters · 2019Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Little is known about mammalian preRC stoichiometry, the number of preRCs on chromosomes, and how this relates to replicon size and usage. We show here that, on average, each 100-kb of the mammalian genome contains a preRC composed of approximately one ORC hexamer, 4-5 MCM hexamers, and 2 Cdc6. Relative to these subunits, ∼0.35 total molecules of the pre-Initiation Complex factor Cdc45 are present. Thus, based on ORC availability, somatic cells contain ∼70,000 preRCs of this average total stoichiometry, although subunits may not be juxtaposed with each other. Except for ORC, the chromatin-bound complement of preRC subunits is even lower. Cdc45 is present at very low levels relative to the preRC subunits, but is highly stable, and the same limited number of stable Cdc45 molecules are present from the beginning of S-phase to its completion. Efforts to artificially increase Cdc45 levels through ectopic expression block cell growth. However, microinjection of excess purified Cdc45 into S-phase nuclei activates additional replication foci by three-fold, indicating that Cdc45 functions to activate dormant preRCs and is rate-limiting for somatic replicon usage. Paradoxically, although Cdc45 colocalizes in vivo with some MCM sites and is rate-limiting for DNA replication to occur, neither Cdc45 nor MCMs colocalize with active replication sites. Embryonic metazoan chromatin consists of small replicons that are used efficiently via an excess of preRC subunits. In contrast, somatic mammalian cells contain a low density of preRCs, each containing only a few MCMs that compete for limiting amounts of Cdc45. This provides a molecular explanation why, relative to embryonic replicon dynamics, somatic replicons are, on average, larger and origin efficiency tends to be lower. The stable, continuous, and rate-limiting nature of Cdc45 suggests that Cdc45 contributes to the staggering of replicon usage throughout S-phase, and that replicon activation requires reutilization of existing Cdc45 during S-phase.
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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.