ArticleOncogene2012
Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart.
Article in Oncogene, 2012. 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 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells.Nucleic acids research · 2023Article
- SETMAR, a case of primate co-opted genes: towards new perspectives.Mobile DNA · 2022Review
- Article
- Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy.Frontiers in oncology · 2022Review
- Structure, Activity, and Function of SETMAR Protein Lysine Methyltransferase.Life (Basel, Switzerland) · 2021Review
- A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1.Molecular and cellular biology · 2021Article
- Genome Maintenance Mechanisms at the Chromatin Level.International journal of molecular sciences · 2021Review
- Review
- Chk1 promotes non-homologous end joining in G1 through direct phosphorylation of ASF1A.Cell reports · 2021Article
- Distinct roles of structure-specific endonucleases EEPD1 and Metnase in replication stress responses.NAR cancer · 2020Article
- The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair.DNA repair · 2019Article
- Article
- Pyruvate kinase M2 regulates homologous recombination-mediated DNA double-strand break repair.Cell research · 2018Article
- Histone methylation in DNA repair and clinical practice: new findings during the past 5-years.Journal of Cancer · 2018Review
- Paths from DNA damage and signaling to genome rearrangements via homologous recombination.Mutation research · 2017Review
- SETMAR isoforms in glioblastoma: A matter of protein stability.Oncotarget · 2017Article
- Metnase Mediates Loading of Exonuclease 1 onto Single Strand Overhang DNA for End Resection at Stalled Replication Forks.The Journal of biological chemistry · 2017Article
- Recovery from the DNA Replication Checkpoint.Genes · 2016Review
- EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair.PLoS genetics · 2015Article
- A Proteomic Strategy Identifies Lysine Methylation of Splicing Factor snRNP70 by the SETMAR Enzyme.The Journal of biological chemistry · 2015Article
Corrections and comments
- Erratum issuedLaitao, A [corrected to Leitao, A]
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Chk1 both arrests replication forks and enhances repair of DNA damage by phosphorylating downstream effectors. Although there has been a concerted effort to identify effectors of Chk1 activity, underlying mechanisms of effector action are still being identified. Metnase (also called SETMAR) is a SET and transposase domain protein that promotes both DNA double-strand break (DSB) repair and restart of stalled replication forks. In this study, we show that Metnase is phosphorylated only on Ser495 (S495) in vivo in response to DNA damage by ionizing radiation. Chk1 is the major mediator of this phosphorylation event. We had previously shown that wild-type (wt) Metnase associates with chromatin near DSBs and methylates histone H3 Lys36. Here we show that a Ser495Ala (S495A) Metnase mutant, which is not phosphorylated by Chk1, is defective in DSB-induced chromatin association. The S495A mutant also fails to enhance repair of an induced DSB when compared with wt Metnase. Interestingly, the S495A mutant demonstrated increased restart of stalled replication forks compared with wt Metnase. Thus, phosphorylation of Metnase S495 differentiates between these two functions, enhancing DSB repair and repressing replication fork restart. In summary, these data lend insight into the mechanism by which Chk1 enhances repair of DNA damage while at the same time repressing stalled replication fork restart.
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.