ArticleGenes & development2015
Sequential replication-coupled destruction at G1/S ensures genome stability.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 55 citations in OpenAlex.
- Stability of c-Myc Protein in Early S Phase Is Regulated by the Interaction with PCNA.International journal of molecular sciences · 2026Article
- Structure-guided analysis and prediction of human E2-E3 ligase pairing specificity.bioRxiv : the preprint server for biology · 2026Article
- RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor.Scientific reports · 2024Article
- Differential endothelial cell cycle status in postnatal retinal vessels revealed using a novel PIP-FUCCI reporter and zonation analysis.Angiogenesis · 2024Article
- Cell identity revealed by precise cell cycle state mapping links data modalities.bioRxiv : the preprint server for biology · 2024Article
- Cell cycle plasticity underlies fractional resistance to palbociclib in ER+/HER2- breast tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Differential endothelial cell cycle status in postnatal retinal vessels revealed using a novel PIP-FUCCI reporter and zonation analysis.bioRxiv : the preprint server for biology · 2024Article
- Daughter cell fate choice instructed preemptively by mother cells facing nutrient limitation.iScience · 2023Article
- Long-term p21 and p53 dynamics regulate the frequency of mitosis events and cell cycle arrest following radiation damage.Cell death and differentiation · 2023Article
- Revisiting the Function of p21International journal of molecular sciences · 2022Review
- Disrupted control of origin activation compromises genome integrity upon destabilization of Polε and dysfunction of the TRP53-CDKN1A/P21 axis.Cell reports · 2022Article
- USP7 and VCPCell reports · 2021Article
- Dynamics of replication origin over-activation.Nature communications · 2021Article
- Clinical CDK4/6 inhibitors induce selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2.Nature communications · 2021Article
- Article
- 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
- Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding.Nucleic acids research · 2020Article
- Review
- The RepID-CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation.Nature communications · 2020Article
- DNA replication and mitotic entry: A brake model for cell cycle progression.The Journal of cell biology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Timely ubiquitin-mediated protein degradation is fundamental to cell cycle control, but the precise degradation order at each cell cycle phase transition is still unclear. We investigated the degradation order among substrates of a single human E3 ubiquitin ligase, CRL4(Cdt2), which mediates the S-phase degradation of key cell cycle proteins, including Cdt1, PR-Set7, and p21. Our analysis of synchronized cells and asynchronously proliferating live single cells revealed a consistent order of replication-coupled destruction during both S-phase entry and DNA repair; Cdt1 is destroyed first, whereas p21 destruction is always substantially later than that of Cdt1. These differences are attributable to the CRL4(Cdt2) targeting motif known as the PIP degron, which binds DNA-loaded proliferating cell nuclear antigen (PCNA(DNA)) and recruits CRL4(Cdt2). Fusing Cdt1's PIP degron to p21 causes p21 to be destroyed nearly concurrently with Cdt1 rather than consecutively. This accelerated degradation conferred by the Cdt1 PIP degron is accompanied by more effective Cdt2 recruitment by Cdt1 even though p21 has higher affinity for PCNA(DNA). Importantly, cells with artificially accelerated p21 degradation display evidence of stalled replication in mid-S phase and sensitivity to replication arrest. We therefore propose that sequential degradation ensures orderly S-phase progression to avoid replication stress and genome instability.
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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.