ArticleProceedings of the National Academy of Sciences of the United States of America2022
Transcription-replication conflicts in primordial germ cells necessitate the Fanconi anemia pathway to safeguard genome stability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 58 citations in OpenAlex.
- Single-cell mapping of chromosome breaks identifies multiple fragile site classes with distinct DNA replication timing landscapes.Nature communications · 2026Article
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- MCM8-9 helicase activity protects primordial germ cell development to prevent premature ovarian insufficiency.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The landscape and regulatory potential of eccDNAs in mammalian preimplantation embryos.Nature communications · 2026Article
- RAD51C-XRCC3 complex regulates FANCM-mediated R-loop resolution to safeguard genome integrity.Science advances · 2026Article
- Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026Review
- The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts.Nucleic acids research · 2026Article
- Tatdn2 is required for DNA repair to safeguard genome stability in primordial germ cells.Nucleic acids research · 2025Article
- Biallelic BRCA2 variants induce premature ovarian insufficiency by impaired meiotic homologous recombination.Communications biology · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- Wdr5-mediated H3K4 methylation facilitates HSPC development via maintenance of genomic stability in zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genome-wide landscape of miRNA-mRNA-lncRNA-circRNA ceRNA network in Nanos2 deficient mice.PloS one · 2025Article
- Premature ovarian insufficiency.Nature reviews. Disease primers · 2024Review
- Depletion of placental brain-derived neurotrophic factor (BDNF) is attributed to premature ovarian insufficiency (POI) in mice offspring.Journal of ovarian research · 2024Article
- MCM8 interacts with DDX5 to promote R-loop resolution.The EMBO journal · 2024Article
- LUC7L3 is a downstream factor of SRSF1 and prevents genomic instability.Cell insight · 2024Article
- [Homozygous Variant ofSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- Primordial germ cell DNA demethylation and development require DNA translesion synthesis.Nature communications · 2024Article
- RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.The Journal of clinical investigation · 2024Article
- Novel compound heterozygous variants in FANCI cause premature ovarian insufficiency.Human genetics · 2024Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preserving a high degree of genome integrity and stability in germ cells is of utmost importance for reproduction and species propagation. However, the regulatory mechanisms of maintaining genome stability in the developing primordial germ cells (PGCs), in which rapid proliferation is coupled with global hypertranscription, remain largely unknown. Here, we find that mouse PGCs encounter a constitutively high frequency of transcription-replication conflicts (TRCs), which lead to R-loop accumulation and impose endogenous replication stress on PGCs. We further demonstrate that the Fanconi anemia (FA) pathway is activated by TRCs and has a central role in the coordination between replication and transcription in the rapidly proliferating PGCs, as disabling the FA pathway leads to TRC and R-loop accumulation, replication fork destabilization, increased DNA damage, dramatic loss of mitotically dividing mouse PGCs, and consequent sterility of both sexes. Overall, our findings uncover the unique source and resolving mechanism of endogenous replication stress during PGC proliferation, provide a biological explanation for reproductive defects in individuals with FA, and improve our understanding of the monitoring strategies for genome stability during germ cell development.
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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.