ArticleProceedings of the National Academy of Sciences of the United States of America2021
SETD2-mediated H3K14 trimethylation promotes ATR activation and stalled replication fork restart in response to DNA replication stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Histone modification cross talk between a host and pathogen.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- AURORA A interacts with DICER and SETD2 to promote S-phase progression.EMBO reports · 2026Article
- Histone 3 lysine 36 trimethylation by SETD2 shapes an epigenetic landscape in intestinal stem cells to orchestrate lipid metabolism and attenuate cell senescence.Cell death & disease · 2026Article
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- Emerging role of SETD2 in the development and function of immune cells.Genes & diseases · 2025Review
- Loss of SETD2 in wild-type VHL clear cell renal cell carcinoma sensitizes cells to STF-62247 and leads to DNA damage, cell cycle arrest, and cell death characteristic of pyroptosis.Molecular oncology · 2025Article
- H3K14: A histone site closely related to diseases.Journal of Cancer · 2025Review
- Review
- CK2-dependent degradation of CBX3 dictates replication fork stalling and PARP inhibitor sensitivity.Science advances · 2024Article
- Targeting ATR in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- The SETD2 Methyltransferase Supports Productive HPV31 Replication through the LEDGF/CtIP/Rad51 Pathway.Journal of virology · 2023Article
- Legionella para-effectors target chromatin and promote bacterial replication.Nature communications · 2023Article
- Spore Oil-Functionalized Selenium Nanoparticles Protect Pancreatic Beta Cells from Palmitic Acid-Induced Apoptosis via Inhibition of Oxidative Stress-Mediated Apoptotic Pathways.Antioxidants (Basel, Switzerland) · 2023Article
- Protective effect of spore oil-functionalized nano-selenium system on cisplatin-induced nephrotoxicity by regulating oxidative stress-mediated pathways and activating immune response.Journal of nanobiotechnology · 2023Article
- Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma.Frontiers in oncology · 2023Review
- Mechanisms of germ cell survival and plasticity in Caenorhabditis elegans.Biochemical Society transactions · 2022Review
- SETD2: from chromatin modifier to multipronged regulator of the genome and beyond.Cellular and molecular life sciences : CMLS · 2022Review
- Review
- Novel insight into mechanisms for ATR activation by chromatin structures.Archives of toxicology · 2021Article
- The Role of γH2AX in Replication Stress-induced Carcinogenesis: Possible Links and Recent Developments.Cancer diagnosis & prognosisReview
Corrections and comments
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- Erratum issued
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ataxia telangiectasia and Rad3 related (ATR) activation after replication stress involves a cascade of reactions, including replication protein A (RPA) complex loading onto single-stranded DNA and ATR activator loading onto chromatin. The contribution of histone modifications to ATR activation, however, is unclear. Here, we report that H3K14 trimethylation responds to replication stress by enhancing ATR activation. First, we confirmed that H3K14 monomethylation, dimethylation, and trimethylation all exist in mammalian cells, and that both SUV39H1 and SETD2 methyltransferases can catalyze H3K14 trimethylation in vivo and in vitro. Interestingly, SETD2-mediated H3K14 trimethylation markedly increases in response to replication stress induced with hydroxyurea, a replication stress inducer. Under these conditions, SETD2-mediated H3K14me3 recruited the RPA complex to chromatin via a direct interaction with RPA70. The increase in H3K14me3 levels was abolished, and RPA loading was attenuated when SETD2 was depleted or H3K14 was mutated. Rather, the cells were sensitive to replication stress such that the replication forks failed to restart, and cell-cycle progression was delayed. These findings help us understand how H3K14 trimethylation links replication stress with ATR activation.
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