ArticleNucleic acids research2022
Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Accelerating tumor evolution and enhancing immunotherapy efficacy in lung adenocarcinoma based on EXO1 inhibition.Translational lung cancer research · 2026Article
- Article
- The Experimental Procedure of Somatic Hypermutation Analysis in Splenic B Cells During Primary Response.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment:International journal of molecular sciences · 2025Article
- Insight into meiotic DNA end resection: Mechanisms and regulation.DNA repair · 2025Review
- EXO1 promotes the meiotic MLH1-MLH3 endonuclease through conserved interactions with MLH1, MSH4 and DNA.Nature communications · 2025Article
- Cancer cells' chamber of secrets: the link between micronuclei, chromothripsis and malignancy.Open biology · 2025Review
- Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection.Nature communications · 2025Article
- EXO1's pan-cancer roles: diagnostic, prognostic, and immunological analyses through bioinformatics.Discover oncology · 2025Article
- Identification of EXO1 as a potential biomarker associated with prognosis and tumor immune microenvironment for specific human cancers.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Intercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation.Journal of extracellular vesicles · 2025Article
- Structure-specific nucleases in genome dynamics and strategies for targeting cancers.Journal of molecular cell biology · 2024Review
- Divergence and conservation of the meiotic recombination machinery.Nature reviews. Genetics · 2024Review
- Modular cytosine base editing promotes epigenomic and genomic modifications.Nucleic acids research · 2024Article
- The bioinformatics analysis and experimental validation of the carcinogenic role of EXO1 in lung adenocarcinoma.Frontiers in oncology · 2024Article
- Genetic dissection of crossover mutants defines discrete intermediates in mouse meiosis.Molecular cell · 2023Article
- Genome-Wide Analysis of Sheep Artificially or Naturally Infected with Gastrointestinal Nematodes.Genes · 2023Article
- Exo1 protects DNA nicks from ligation to promote crossover formation during meiosis.PLoS biology · 2023Article
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Authors and funding
15 authors at 9 institutions in 4 countries.
Funding
Abstract
DNA damage response pathways rely extensively on nuclease activity to process DNA intermediates. Exonuclease 1 (EXO1) is a pleiotropic evolutionary conserved DNA exonuclease involved in various DNA repair pathways, replication, antibody diversification, and meiosis. But, whether EXO1 facilitates these DNA metabolic processes through its enzymatic or scaffolding functions remains unclear. Here, we dissect the contribution of EXO1 enzymatic versus scaffolding activity by comparing Exo1DA/DA mice expressing a proven nuclease-dead mutant form of EXO1 to entirely EXO1-deficient Exo1-/- and EXO1 wild type Exo1+/+ mice. We show that Exo1DA/DA and Exo1-/- mice are compromised in canonical DNA repair processing, suggesting that the EXO1 enzymatic role is important for error-free DNA mismatch and double-strand break repair pathways. However, in non-canonical repair pathways, EXO1 appears to have a more nuanced function. Next-generation sequencing of heavy chain V region in B cells showed the mutation spectra of Exo1DA/DA mice to be intermediate between Exo1+/+ and Exo1-/- mice, suggesting that both catalytic and scaffolding roles of EXO1 are important for somatic hypermutation. Similarly, while overall class switch recombination in Exo1DA/DA and Exo1-/- mice was comparably defective, switch junction analysis suggests that EXO1 might fulfill an additional scaffolding function downstream of class switching. In contrast to Exo1-/- mice that are infertile, meiosis progressed normally in Exo1DA/DA and Exo1+/+ cohorts, indicating that a structural but not the nuclease function of EXO1 is critical for meiosis. However, both Exo1DA/DA and Exo1-/- mice displayed similar mortality and cancer predisposition profiles. Taken together, these data demonstrate that EXO1 has both scaffolding and enzymatic functions in distinct DNA repair processes and suggest a more composite and intricate role for EXO1 in DNA metabolic processes and disease.
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