ArticleThe Journal of biological chemistry2012
Human exonuclease 5 is a novel sliding exonuclease required for genome stability.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Integrative Computational Analysis of Common EXO5 Haplotypes: Impact on Protein Dynamics, Genome Stability, and Cancer Progression.Journal of chemical information and modeling · 2025Article
- A Plasmodium apicoplast-targeted unique exonuclease/FEN exhibits interspecies functional differences attributable to an insertion that alters DNA-binding.Nucleic acids research · 2024Article
- Genetic Factors and Long-term Treatment-Related Neurocognitive Deficits, Anxiety, and Depression in Childhood Leukemia Survivors: An Exome-Wide Association Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Review
- Blockade of neutral sphingomyelinase 2 exerts antitumor effect on metastatic castration resistant prostate cancer cells and promotes tumor regression when combined with Enzalutamide.American journal of cancer research · 2024Article
- Article
- Species-specific partial gene duplication in Arabidopsis thaliana evolved novel phenotypic effects on morphological traits under strong positive selection.The Plant cell · 2022Article
- Co-evolution based machine-learning for predicting functional interactions between human genes.Nature communications · 2021Article
- EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart.Molecular cell · 2021Article
- Decoding Cancer Variants of Unknown Significance for Helicase-Nuclease-RPA Complexes Orchestrating DNA Repair During Transcription and Replication.Frontiers in molecular biosciences · 2021Article
- Implications of Membrane Binding by the Fe-S Cluster-Containing N-Terminal Domain in theFrontiers in genetics · 2021Article
- Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair.Critical reviews in biochemistry and molecular biology · 2020Review
- Functional deficiency of DNA repair gene EXO5 results in androgen-induced genomic instability and prostate tumorigenesis.Oncogene · 2020Article
- The roles of fission yeast exonuclease 5 in nuclear and mitochondrial genome stability.DNA repair · 2019Article
- Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas.Cell reports · 2018Article
- Robust Production, Crystallization, Structure Determination, and Analysis of [Fe-S] Proteins: Uncovering Control of Electron Shuttling and Gating in the Respiratory Metabolism of Molybdopterin Guanine Dinucleotide Enzymes.Methods in enzymology · 2018Article
- RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response.Cell research · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Previously, we characterized Saccharomyces cerevisiae exonuclease 5 (EXO5), which is required for mitochondrial genome maintenance. Here, we identify the human homolog (C1orf176; EXO5) that functions in the repair of nuclear DNA damage. Human EXO5 (hEXO5) contains an iron-sulfur cluster. It is a single-stranded DNA (ssDNA)-specific bidirectional exonuclease with a strong preference for 5'-ends. After loading at an ssDNA end, hEXO5 slides extensively along the ssDNA prior to cutting, hence the designation sliding exonuclease. However, the single-stranded binding protein human replication protein A (hRPA) restricts sliding and enforces a unique, species-specific 5'-directionality onto hEXO5. This specificity is lost with a mutant form of hRPA (hRPA-t11) that fails to interact with hEXO5. hEXO5 localizes to nuclear repair foci in response to DNA damage, and its depletion in human cells leads to an increased sensitivity to DNA-damaging agents, in particular interstrand cross-linking-inducing agents. Depletion of hEXO5 also results in an increase in spontaneous and damage-induced chromosome abnormalities including the frequency of triradial chromosomes, suggesting an additional defect in the resolution of stalled DNA replication forks in hEXO5-depleted cells.
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Registered trials
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.