ArticleThe Journal of biological chemistry2008
Cdt1 and Cdc6 are destabilized by rereplication-induced DNA damage.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
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.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Physiological re-replication during human stem cell differentiation.Cell death discovery · 2026Article
- Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.Molecular cancer · 2024Article
- ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions.Nature communications · 2022Article
- Article
- Review
- Article
- Cdt1 variants reveal unanticipated aspects of interactions with cyclin/CDK and MCM important for normal genome replication.Molecular biology of the cell · 2018Article
- Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress.International journal of molecular sciences · 2018Review
- Article
- Accurate delineation of cell cycle phase transitions in living cells with PIP-FUCCI.Cell cycle (Georgetown, Tex.) · 2018Article
- Geminin deletion in pre-meiotic DNA replication stage causes spermatogenesis defect and infertility.The Journal of reproduction and development · 2017Article
- Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability.Genes · 2016Review
- HUWE1 interacts with PCNA to alleviate replication stress.EMBO reports · 2016Article
- CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.The Journal of biological chemistry · 2015Article
- 14-3-3 proteins play a role in the cell cycle by shielding cdt2 from ubiquitin-mediated degradation.Molecular and cellular biology · 2014Article
- A high ratio of G1 to G0 phase cells and an accumulation of G1 phase cells before S phase progression after injurious stimuli in the proximal tubule.Physiological reports · 2014Article
- Geminin deploys multiple mechanisms to regulate Cdt1 before cell division thus ensuring the proper execution of DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Activation of a human chromosomal replication origin by protein tethering.Nucleic acids research · 2013Article
- The spindle checkpoint, APC/C(Cdc20), and APC/C(Cdh1) play distinct roles in connecting mitosis to S phase.The Journal of cell biology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The replication factors Cdt1 and Cdc6 are essential for origin licensing, a prerequisite for DNA replication initiation. Mechanisms to ensure that metazoan origins initiate once per cell cycle include degradation of Cdt1 during S phase and inhibition of Cdt1 by the geminin protein. Geminin depletion or overexpression of Cdt1 or Cdc6 in human cells causes rereplication, a form of endogenous DNA damage. Rereplication induced by these manipulations is however uneven and incomplete, suggesting that one or more mechanisms restrain rereplication once it begins. We find that both Cdt1 and Cdc6 are degraded in geminin-depleted cells. We further show that Cdt1 degradation in cells that have rereplicated requires the PCNA binding site of Cdt1 and the Cul4(DDB1) ubiquitin ligase, and Cdt1 can induce its own degradation when overproduced. Cdc6 degradation in geminin-depleted cells requires Huwe1, the ubiquitin ligase that regulates Cdc6 after DNA damage. Moreover, perturbations that specifically disrupt Cdt1 and Cdc6 degradation in response to DNA damage exacerbate rereplication when combined with geminin depletion, and this enhanced rereplication occurs in both human cells and in Drosophila melanogaster cells. We conclude that rereplication-associated DNA damage triggers Cdt1 and Cdc6 ubiquitination and destruction, and propose that this pathway represents an evolutionarily conserved mechanism that minimizes the extent of rereplication.
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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.