ArticleCell research2018
Mouse embryonic stem cells have increased capacity for replication fork restart driven by the specific Filia-Floped protein complex.
Article in Cell research, 2018. 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, 38 citations in OpenAlex.
- The antiviral role of TRIM25 in mammalian embryonic stem cells.Virologica Sinica · 2026Article
- Tcf15 promotes an open nucleolar chromatin state to safeguard ribosome biogenesis and genome stability in mouse embryonic stem cells.PLoS biology · 2026Article
- Naïve pluripotency and genomic stability are coordinated in embryonic stem cells by a novel pluripotency regulator ZFP998.Nucleic acids research · 2026Article
- Genes as Genome Stabilizers in Pluripotent Stem Cells.Advances in experimental medicine and biology · 2025Review
- RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2024Article
- Structural basis of the subcortical maternal complex and its implications in reproductive disorders.Nature structural & molecular biology · 2024Article
- Characterization of long-termZoological research · 2023Article
- Review
- Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Article
- DPPA5A suppresses the mutagenic TLS and MMEJ pathways by modulating the cryptic splicing ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells.Stem cell reports · 2023Article
- Article
- Article
- Revealing the expression profile of genes that encode the Subcortical Maternal Complex in human reproductive failures.Genetics and molecular biology · 2023Article
- Expression profiles of meiotic genes in male vs. female gonads and gametes: Insights into fertility issues.Frontiers in genetics · 2023Article
- Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3.Nature communications · 2022Article
- ISG15 conjugation to proteins on nascent DNA mitigates DNA replication stress.Nature communications · 2022Article
- RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- SANA: cross-species prediction of Gene Ontology GO annotations via topological network alignment.NPJ systems biology and applications · 2022Article
- Current understanding of genomic stability maintenancein pluripotent stem cells.Acta biochimica et biophysica Sinica · 2022Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pluripotent stem cells (PSCs) harbor constitutive DNA replication stress during their rapid proliferation and the consequent genome instability hampers their applications in regenerative medicine. It is therefore important to understand the regulatory mechanisms of replication stress response in PSCs. Here, we report that mouse embryonic stem cells (ESCs) are superior to differentiated cells in resolving replication stress. Specifically, ESCs utilize a unique Filia-Floped protein complex-dependent mechanism to efficiently promote the restart of stalled replication forks, therefore maintaining genomic stability. The ESC-specific Filia-Floped complex resides on replication forks under normal conditions. Replication stress stimulates their recruitment to stalling forks and the serine 151 residue of Filia is phosphorylated in an ATR-dependent manner. This modification enables the Filia-Floped complex to act as a functional scaffold, which then promotes the stalling fork restart through a dual mechanism: both enhancing recruitment of the replication fork restart protein, Blm, and stimulating ATR kinase activation. In the Blm pathway, the scaffolds recruit the E3 ubiquitin ligase, Trim25, to the stalled replication forks, and in turn Trim25 tethers and concentrates Blm at stalled replication forks through ubiquitination. In differentiated cells, the recruitment of the Trim25-Blm complex to replication forks and the activation of ATR signaling are much less robust due to lack of the ESC-specific Filia-Floped scaffold. Thus, our study reveals that ESCs utilize an additional and unique regulatory layer to efficiently promote the stalled fork restart and maintain genomic stability.
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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 Socratic graph.