ArticlePLoS genetics2020
Distinct and sequential re-replication barriers ensure precise genome duplication.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Replication origin flexibility: a tool to mitigate the hazards of excess replication.Trends in genetics : TIG · 2026Review
- Geminin inhibits DNA replication licensing by sterically blocking CDT1-MCM2 interactions.Nature communications · 2025Article
- A guide to the apicomplexan cell cycle: endodyogeny and schizogony.Trends in parasitology · 2025Review
- A novel homozygous intronic variant in CDT1 that alters splicing causes Meier-Gorlin syndrome, and a review of published mutations and growth hormone treatments.Orphanet journal of rare diseases · 2024Review
- The Crk4-Cyc4 complex regulates GThe EMBO journal · 2024Article
- RAD51 restricts DNA over-replication from re-activated origins.The EMBO journal · 2024Article
- Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023Review
- The Ndc80-Cdt1-Ska1 complex is a central processive kinetochore-microtubule coupling unit.The Journal of cell biology · 2023Article
- Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation.Nature structural & molecular biology · 2023Article
- CDT1, a licensing factor that limits rereplication.Molecular cell · 2023Article
- CDT1 inhibits CMG helicase in early S phase to separate origin licensing from DNA synthesis.Molecular cell · 2023Article
- Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions.Nature communications · 2022Article
- Persistent DNA damage underlies tubular cell polyploidization and progression to chronic kidney disease in kidneys deficient in the DNA repair protein FAN1.Kidney international · 2022Article
- Quantitative profiling of adaptation to cyclin E overproduction.Life science alliance · 2022Article
- Preventing excess replication origin activation to ensure genome stability.Trends in genetics : TIG · 2022Review
- Small Molecule Inhibitor Targeting CDT1/Geminin Protein Complex Promotes DNA Damage and Cell Death in Cancer Cells.Frontiers in pharmacology · 2022Article
- Replication initiation: Implications in genome integrity.DNA repair · 2021Review
- Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.Molecular cell · 2021Article
- Stabilisation of half MCM ring by Cdt1 during DNA insertion.Nature communications · 2021Article
- SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Achieving complete and precise genome duplication requires that each genomic segment be replicated only once per cell division cycle. Protecting large eukaryotic genomes from re-replication requires an overlapping set of molecular mechanisms that prevent the first DNA replication step, the DNA loading of MCM helicase complexes to license replication origins, after S phase begins. Previous reports have defined many such origin licensing inhibition mechanisms, but the temporal relationships among them are not clear, particularly with respect to preventing re-replication in G2 and M phases. Using a combination of mutagenesis, biochemistry, and single cell analyses in human cells, we define a new mechanism that prevents re-replication through hyperphosphorylation of the essential MCM loading protein, Cdt1. We demonstrate that Cyclin A/CDK1 can hyperphosphorylate Cdt1 to inhibit MCM re-loading in G2 phase. The mechanism of inhibition is to block Cdt1 binding to MCM independently of other known Cdt1 inactivation mechanisms such as Cdt1 degradation during S phase or Geminin binding. Moreover, our findings suggest that Cdt1 dephosphorylation at the mitosis-to-G1 phase transition re-activates Cdt1. We propose that multiple distinct, non-redundant licensing inhibition mechanisms act in a series of sequential relays through each cell cycle phase to ensure precise genome duplication.
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Registered trials
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.