ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
- Redundant mispair excision mechanisms in eukaryotic DNA mismatch repair.Nucleus (Austin, Tex.) · 2026Review
- Minor spliceosome inhibition via ablation of its U11 snRNA gene results in multiple defects in murine spermatogenesis.Nucleic acids research · 2026Article
- Article
- EXO1 promotes the meiotic MLH1-MLH3 endonuclease through conserved interactions with MLH1, MSH4 and DNA.Nature communications · 2025Article
- EXO1's pan-cancer roles: diagnostic, prognostic, and immunological analyses through bioinformatics.Discover oncology · 2025Article
- EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.Nucleic acids research · 2024Article
- In vivo versus in silico assessment of potentially pathogenic missense variants in human reproductive genes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene.Nature communications · 2023Article
- Article
- Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice.Nucleic acids research · 2022Article
- Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer.Cells · 2022Review
- Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.Human reproduction (Oxford, England) · 2022Article
- SLX4 dampens MutSα-dependent mismatch repair.Nucleic acids research · 2022Article
- Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1.Genetics and molecular biology · 2022Article
- Genome Replication Is Associated With Release of Immunogenic DNA Waste.Frontiers in immunology · 2022Article
- Multiple DSB Resection Activities Redundantly Promote Alternative End Joining-Mediated Class Switch Recombination.Frontiers in cell and developmental biology · 2021Article
- Specific Human ATR and ATM Inhibitors Modulate Single Strand DNA Formation inFrontiers in cellular and infection microbiology · 2021Article
- Elevated EXO1 expression is associated with breast carcinogenesis and poor prognosis.Annals of translational medicine · 2021Article
- Exo1 recruits Cdc5 polo kinase to MutLγ to ensure efficient meiotic crossover formation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Mammalian Exonuclease 1 (EXO1) is an evolutionarily conserved, multifunctional exonuclease involved in DNA damage repair, replication, immunoglobulin diversity, meiosis, and telomere maintenance. It has been assumed that EXO1 participates in these processes primarily through its exonuclease activity, but recent studies also suggest that EXO1 has a structural function in the assembly of higher-order protein complexes. To dissect the enzymatic and nonenzymatic roles of EXO1 in the different biological processes in vivo, we generated an EXO1-E109K knockin (Exo1(EK)) mouse expressing a stable exonuclease-deficient protein and, for comparison, a fully EXO1-deficient (Exo1(null)) mouse. In contrast to Exo1(null/null) mice, Exo1(EK/EK) mice retained mismatch repair activity and displayed normal class switch recombination and meiosis. However, both Exo1-mutant lines showed defects in DNA damage response including DNA double-strand break repair (DSBR) through DNA end resection, chromosomal stability, and tumor suppression, indicating that the enzymatic function is required for those processes. On a transformation-related protein 53 (Trp53)-null background, the DSBR defect caused by the E109K mutation altered the tumor spectrum but did not affect the overall survival as compared with p53-Exo1(null) mice, whose defects in both DSBR and mismatch repair also compromised survival. The separation of these functions demonstrates the differential requirement for the structural function and nuclease activity of mammalian EXO1 in distinct DNA repair processes and tumorigenesis in vivo.
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