ArticleThe Journal of biological chemistry2014
The DDN catalytic motif is required for Metnase functions in non-homologous end joining (NHEJ) repair and replication restart.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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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
26 citing papers in PubMed, 40 citations in OpenAlex.
- Epistasis between mutator alleles contributes to germline mutation spectrum variability in laboratory mice.eLife · 2024Article
- Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023Review
- Epistasis between mutator alleles contributes to germline mutation spectra variability in laboratory mice.bioRxiv : the preprint server for biology · 2023Article
- Roles of homologous recombination in response to ionizing radiation-induced DNA damage.International journal of radiation biology · 2023Review
- Structural and genome-wide analyses suggest that transposon-derived protein SETMAR alters transcription and splicing.The Journal of biological chemistry · 2022Article
- 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
- Article
- The Safe Path at the Fork: Ensuring Replication-Associated DNA Double-Strand Breaks are Repaired by Homologous Recombination.Frontiers in genetics · 2021Review
- Distinct roles of structure-specific endonucleases EEPD1 and Metnase in replication stress responses.NAR cancer · 2020Article
- The Tc1-like elements with the spliceosomal introns in mollusk genomes.Molecular genetics and genomics : MGG · 2020Article
- The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair.DNA repair · 2019Article
- Article
- Paths from DNA damage and signaling to genome rearrangements via homologous recombination.Mutation research · 2017Review
- The endonuclease EEPD1 mediates synthetic lethality in RAD52-depleted BRCA1 mutant breast cancer cells.Breast cancer research : BCR · 2017Article
- Drugging the Cancers Addicted to DNA Repair.Journal of the National Cancer Institute · 2017Review
- Translational research in radiation-induced DNA damage signaling and repair.Translational cancer research · 2017Article
- Endonuclease EEPD1 Is a Gatekeeper for Repair of Stressed Replication Forks.The Journal of biological chemistry · 2017Article
- SETMAR isoforms in glioblastoma: A matter of protein stability.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Metnase (or SETMAR) arose from a chimeric fusion of the Hsmar1 transposase downstream of a protein methylase in anthropoid primates. Although the Metnase transposase domain has been largely conserved, its catalytic motif (DDN) differs from the DDD motif of related transposases, which may be important for its role as a DNA repair factor and its enzymatic activities. Here, we show that substitution of DDN(610) with either DDD(610) or DDE(610) significantly reduced in vivo functions of Metnase in NHEJ repair and accelerated restart of replication forks. We next tested whether the DDD or DDE mutants cleave single-strand extensions and flaps in partial duplex DNA and pseudo-Tyr structures that mimic stalled replication forks. Neither substrate is cleaved by the DDD or DDE mutant, under the conditions where wild-type Metnase effectively cleaves ssDNA overhangs. We then characterized the ssDNA-binding activity of the Metnase transposase domain and found that the catalytic domain binds ssDNA but not dsDNA, whereas dsDNA binding activity resides in the helix-turn-helix DNA binding domain. Substitution of Asn-610 with either Asp or Glu within the transposase domain significantly reduces ssDNA binding activity. Collectively, our results suggest that a single mutation DDN(610) → DDD(610), which restores the ancestral catalytic site, results in loss of function in Metnase.
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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.