ArticleGenes & development2005
Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts.
Article in Genes & development, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 198 citations in OpenAlex.
- CDT1 acts with the replisome to remodel replication forks.Science advances · 2026Article
- Structural obstruction to full DNA replication in terminally differentiated skeletal muscle cells.EMBO reports · 2025Article
- Single-molecule imaging reveals the mechanism of bidirectional replication initiation in metazoa.Cell · 2024Article
- The cohesin modifier ESCO2 is stable during DNA replication.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 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
- Disruption of Toxoplasma gondii-Induced Host Cell DNA Replication Is Dependent on Contact Inhibition and Host Cell Type.mSphere · 2022Article
- Quantitative profiling of adaptation to cyclin E overproduction.Life science alliance · 2022Article
- Approaches to Monitor Termination of DNA Replication Using Xenopus Egg Extracts.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Dynamics of replication origin over-activation.Nature communications · 2021Article
- Single-cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree.eLife · 2021Article
- The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.Molecular cell · 2021Article
- Distinct and sequential re-replication barriers ensure precise genome duplication.PLoS genetics · 2020Article
- E2F-dependent transcription determines replication capacity and S phase length.Nature communications · 2020Article
- Cell Cycle-Dependent Switch of TopBP1 Functions by Cdk2 and Akt.Molecular and cellular biology · 2020Article
- Control of Eukaryotic DNA Replication Initiation-Mechanisms to Ensure Smooth Transitions.Genes · 2019Review
- Article
- Cdt1 variants reveal unanticipated aspects of interactions with cyclin/CDK and MCM important for normal genome replication.Molecular biology of the cell · 2018Article
- The Neddylation Inhibitor Pevonedistat (MLN4924) Suppresses and Radiosensitizes Head and Neck Squamous Carcinoma Cells and Tumors.Molecular cancer therapeutics · 2018Article
- Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotes, prereplication complexes (pre-RCs) containing ORC, Cdc6, Cdt1, and MCM2-7 are assembled on chromatin in the G1 phase. In S phase, when DNA replication initiates, pre-RCs are disassembled, and new pre-RC assembly is restricted until the following G1 period. As a result, DNA replication is limited to a single round per cell cycle. One inhibitor of pre-RC assembly, geminin, was discovered in Xenopus, and it binds and inactivates Cdt1 in S phase. However, removal of geminin from Xenopus egg extracts is insufficient to cause rereplication, suggesting that other safeguards against rereplication exist. Here, we show that Cdt1 is completely degraded by ubiquitin-mediated proteolysis during the course of the first round of DNA replication in Xenopus egg extracts. Degradation depends on Cdk2/Cyclin E, Cdc45, RPA, and polymerase alpha, demonstrating a requirement for replication initiation. Cdt1 is ubiquitinated on chromatin, and this process also requires replication initiation. Once replication has initiated, Cdk2/Cyclin E is dispensable for Cdt1 degradation. When fresh Cdt1 is supplied after the first round of DNA replication, significant rereplication results, and rereplication is enhanced in the absence of geminin. Our results identify a replication-dependent proteolytic pathway that targets Cdt1 and that acts redundantly with geminin to inactivate Cdt1 in S phase.
Indexed as
Identifiers
What OpenQuestion holds
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.