ArticlePLoS genetics2019
The demethylase NMAD-1 regulates DNA replication and repair in the Caenorhabditis elegans germline.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
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- Structural Basis of Nucleic Acid Recognition and 6mA Demethylation byInternational journal of molecular sciences · 2024Article
- Miniature spatial transcriptomics for studying parasite-endosymbiont relationships at the micro scale.Nature communications · 2023Article
- Emerging Roles for DNA 6mA and RNA m6A Methylation in Mammalian Genome.International journal of molecular sciences · 2023Review
- Downregulation of transposable elements extends lifespan in Caenorhabditis elegans.Nature communications · 2023Article
- Caenorhabditis elegans NMAD-1 functions as a demethylase for actin.Journal of molecular cell biology · 2023Article
- Mammalian DNA NMolecular cell · 2023Review
- Means, mechanisms and consequences of adenine methylation in DNA.Nature reviews. Genetics · 2022Review
- N6-methyladenine: A Rare and Dynamic DNA Mark.Advances in experimental medicine and biology · 2022Article
- DNA Methylation on N6-Adenine Regulates the Hyphal Development during Dimorphism in the Early-Diverging FungusJournal of fungi (Basel, Switzerland) · 2021Article
- ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer.Scientific reports · 2021Article
- Topoisomerases Modulate the Timing of Meiotic DNA Breakage and Chromosome Morphogenesis inGenetics · 2020Article
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Authors and funding
12 authors at 3 institutions in 1 country.
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Abstract
The biological roles of nucleic acid methylation, other than at the C5-position of cytosines in CpG dinucleotides, are still not well understood. Here, we report genetic evidence for a critical role for the putative DNA demethylase NMAD-1 in regulating meiosis in C. elegans. nmad-1 mutants have reduced fertility. They show defects in prophase I of meiosis, which leads to reduced embryo production and an increased incidence of males due to defective chromosomal segregation. In nmad-1 mutant worms, nuclear staging beginning at the leptotene and zygotene stages is disorganized, the cohesin complex is mislocalized at the diplotene and diakinesis stages, and chromosomes are improperly condensed, fused, or lost by the end of diakinesis. RNA sequencing of the nmad-1 germline revealed reduced induction of DNA replication and DNA damage response genes during meiosis, which was coupled with delayed DNA replication, impaired DNA repair and increased apoptosis of maturing oocytes. To begin to understand how NMAD-1 regulates DNA replication and repair, we used immunoprecipitation and mass spectrometry to identify NMAD-1 binding proteins. NMAD-1 binds to multiple proteins that regulate DNA repair and replication, including topoisomerase TOP-2 and co-localizes with TOP-2 on chromatin. Moreover, the majority of TOP-2 binding to chromatin depends on NMAD-1. These results suggest that NMAD-1 functions at DNA replication sites to regulate DNA replication and repair during meiosis.
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