ArticleThe EMBO journal2024
MCM8 interacts with DDX5 to promote R-loop resolution.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Critical roles of MCM8 in meiotic recombination during mouse spermatogenesis.bioRxiv : the preprint server for biology · 2026Article
- 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
- Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026Review
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- Targeting WEE1 in ARID1A/TP53 Concurrent Mutant Colorectal Cancer by Exploiting R-Loop Accumulation and DNA Repair Deficiencies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MCM8 variants in two patients with primary ovarian insufficiency: clinical findings andFrontiers in endocrinology · 2026Article
- MTUS2-AS1 suppression promotes DDX5 protein degradation to enhance the sensitivity of PARP inhibitors in BRCA-wild triple negative breast cancer.International journal of biological sciences · 2026Article
- The role of R-loop aberrations in lower-grade gliomas: prognostic, immune, and metabolic implications from multi-omics and machine learning analysis.Frontiers in immunology · 2026Article
- Tatdn2 is required for DNA repair to safeguard genome stability in primordial germ cells.Nucleic acids research · 2025Article
- Uli-epic: profiling RNA modifications from ultra-low input samples.Genome biology · 2025Article
- HELQ Maintains Genome Stability of Primordial Germ Cells by Inhibiting LINE-1 Expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- AmNA-Modified Antisense Oligonucleotide Targeting MCM8 as a Cancer-Specific Chemosensitizer for Platinum Compounds.Cancer science · 2025Article
- A novel homozygous frameshift mutation in MCM8 causes primary gonadal dysgenesis in both genders.Journal of assisted reproduction and genetics · 2025Article
- R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
11 authors.
Funding
Abstract
MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.
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