ArticleMolecular cell2010
CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase.
Article in Molecular cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
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Who cites it
154 citing papers in PubMed, 222 citations in OpenAlex.
- SGSS05-NS3, a covalent SETD8 inhibitor that activates p53 pathway in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Multiple functions of the lysine methyltransferase KMT5a in cancer: potential targets for innovative therapies.Clinical epigenetics · 2025Review
- The TRIM22-CDT2 axis is the key mediator of the p53-Rb signals in growth control of HPV-positive cervical carcinoma cells.Neoplasia (New York, N.Y.) · 2025Article
- Histone H4 lysine 20 methylation marks genes dynamically regulated during erythroid maturation.Epigenetics & chromatin · 2025Article
- BAHCC1 binds H4K20me1 to facilitate the MCM complex loading and DNA replication.Nature communications · 2025Article
- The Condensin II complex regulates essential gene expression programs during erythropoiesis.Development (Cambridge, England) · 2025Article
- Review
- Histone lysine methylation modifiers controlled by protein stability.Experimental & molecular medicine · 2024Review
- Endonucleosis mediates internalization of cytoplasm into the nucleus.Nature communications · 2024Article
- Beyond the tail: the consequence of context in histone post-translational modification and chromatin research.The Biochemical journal · 2024Article
- DCAF14 regulates CDT2 to promote SET8-dependent replication fork protection.Life science alliance · 2024Article
- BRD4770 inhibits vascular smooth muscle cell proliferation via SUV39H2, but not EHMT2 to protect against neointima formation.Human cell · 2023Article
- Article
- Poly ADP-ribosylation of SET8 leads to aberrant H4K20 methylation in mammalian nuclear genome.Communications biology · 2022Article
- Adaptive exchange sustains cullin-RING ubiquitin ligase networks and proper licensing of DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Role of the TSK/TONSL-H3.1 Pathway in Maintaining Genome Stability in Multicellular Eukaryotes.International journal of molecular sciences · 2022Review
- Article
- Distinct developmental phenotypes result from mutation of Set8/KMT5A and histone H4 lysine 20 in Drosophila melanogaster.Genetics · 2022Article
- CRL4Genes · 2022Review
- DTL Is a Prognostic Biomarker and Promotes Bladder Cancer Progression through Regulating the AKT/mTOR axis.Oxidative medicine and cellular longevity · 2022Article
94 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The proper coordination between DNA replication and mitosis during cell-cycle progression is crucial for genomic stability. During G2 and mitosis, Set8 catalyzes monomethylation of histone H4 on lysine 20 (H4K20me1), which promotes chromatin compaction. Set8 levels decline in S phase, but why and how this occurs is unclear. Here, we show that Set8 is targeted for proteolysis in S phase and in response to DNA damage by the E3 ubiquitin ligase, CRL4(Cdt2). Set8 ubiquitylation occurs on chromatin and is coupled to DNA replication via a specific degron in Set8 that binds PCNA. Inactivation of CRL4(Cdt2) leads to Set8 stabilization and aberrant H4K20me1 accumulation in replicating cells. Transient S phase expression of a Set8 mutant lacking the degron promotes premature H4K20me1 accumulation and chromatin compaction, and triggers a checkpoint-mediated G2 arrest. Thus, CRL4(Cdt2)-dependent destruction of Set8 in S phase preserves genome stability by preventing aberrant chromatin compaction during DNA synthesis.
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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.