ArticleProceedings of the National Academy of Sciences of the United States of America2017
DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- SYCP2 recruits HORMAD2 to chromosome axes for unsynapsed chromatin silencing and synapsis surveillance in meiosis.Nature communications · 2026Article
- Digital Chromosome Banding Reveals Distinct Spatiotemporal Dynamics and Sexual Dimorphism in Meiotic Silencing.bioRxiv : the preprint server for biology · 2026Article
- Argonaute proteins orchestrate Meiotic Sex Chromosome Inactivation and timing of the spermatogenic transcriptional program.PLoS genetics · 2026Article
- Nucleolar migration regulates meiotic sex chromosome inactivation via phase separation during mammalian spermatogenesis.Nature communications · 2026Article
- mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deciphering meiotic chromatin organization by SYCP3.Nucleic acids research · 2025Article
- Genome-wide transcriptional silencing and mRNA stabilization allow the coordinated expression of the meiotic program in mice.Nucleic acids research · 2025Article
- ARID1A governs the silencing of sex-linked transcription during male meiosis in the mouse.eLife · 2024Article
- A TOPBP1 allele causing male infertility uncouples XY silencing dynamics from sex body formation.eLife · 2024Article
- The DNA helicase FANCJ (BRIP1) functions in double strand break repair processing, but not crossover formation during prophase I of meiosis in male mice.PLoS genetics · 2024Article
- Article
- Genetic insights: mapping sex-specific loci in Siamese cobra (Naja kaouthia) sheds light on the putative sex determining region.Genes & genomics · 2024Article
- The DNA helicase FANCJ (BRIP1) functions in Double Strand Break repair processing, but not crossover formation during Prophase I of meiosis in male mice.bioRxiv : the preprint server for biology · 2023Article
- Defining Gene Function in Spermatogonial Stem Cells Through Conditional Knockout Approaches.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Sex body: A nest of protein mixture.Frontiers in cell and developmental biology · 2023Review
- Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation.Nature communications · 2022Article
- Chromosomal synapsis defects can trigger oocyte apoptosis without elevating numbers of persistent DNA breaks above wild-type levels.Nucleic acids research · 2022Article
- Understanding the Underlying Molecular Mechanisms of Meiotic Arrest during In Vitro Spermatogenesis in Rat Prepubertal Testicular Tissue.International journal of molecular sciences · 2022Article
- Utility of Homologous Recombination Deficiency Biomarkers Across Cancer Types.JCO precision oncology · 2022Article
- Article
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Meiotic synapsis and recombination between homologs permits the formation of cross-overs that are essential for generating chromosomally balanced sperm and eggs. In mammals, surveillance mechanisms eliminate meiotic cells with defective synapsis, thereby minimizing transmission of aneuploidy. One such surveillance mechanism is meiotic silencing, the inactivation of genes located on asynapsed chromosomes, via ATR-dependent serine-139 phosphorylation of histone H2AFX (γH2AFX). Stimulation of ATR activity requires direct interaction with an ATR activation domain (AAD)-containing partner. However, which partner facilitates the meiotic silencing properties of ATR is unknown. Focusing on the best-characterized example of meiotic silencing, meiotic sex chromosome inactivation, we reveal this AAD-containing partner to be the DNA damage and checkpoint protein TOPBP1. Conditional TOPBP1 deletion during pachynema causes germ cell elimination associated with defective X chromosome gene silencing and sex chromosome condensation. TOPBP1 is essential for localization to the X chromosome of silencing "sensors," including BRCA1, and effectors, including ATR, γH2AFX, and canonical repressive histone marks. We present evidence that persistent DNA double-strand breaks act as silencing initiation sites. Our study identifies TOPBP1 as a critical factor in meiotic sex chromosome silencing.
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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.