ArticleThe Journal of biological chemistry2012
Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome.
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 57 papers.
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Who cites it
57 citing papers in PubMed, 96 citations in OpenAlex.
- F2,6BP restores mitochondrial genome integrity in Huntington's disease.The Journal of biological chemistry · 2026Article
- Peripheral immune cell-specific genes in Parkinson's disease uncovered by multi-omics with therapeutic implications.NPJ Parkinson's disease · 2025Article
- Dirty Ends: Formation, Repair, and Biological Relevance of Non-Canonical DNA Terminal Structures.Genes · 2025Review
- Huntingtin preserves mitochondrial genome integrity in neurons, which is impaired in Huntington's disease.bioRxiv : the preprint server for biology · 2025Article
- Research progress on the role of the NEIL family in cancer.Frontiers in cell and developmental biology · 2025Review
- Loss of the DNA repair protein, polynucleotide kinase/phosphatase, activates the type 1 interferon response independent of ionizing radiation.Nucleic acids research · 2024Article
- Review
- Functional roles and cancer variants of the bifunctional glycosylase NEIL2.Environmental and molecular mutagenesis · 2024Review
- Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.Nucleic acids research · 2024Article
- Decoding mitochondrial DNA damage and repair associated withFrontiers in cellular and infection microbiology · 2024Review
- Dysregulation of DNA repair genes in Fuchs endothelial corneal dystrophy.Experimental eye research · 2023Article
- Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity.Antioxidants (Basel, Switzerland) · 2023Article
- Highly Sensitive Radioactivity-Based DNA 3'-Phosphatase Activity Assay for Polynucleotide Kinase 3'-Phosphatase.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Dynamic features of human mitochondrial DNA maintenance and transcription.Frontiers in cell and developmental biology · 2022Review
- Beyond base excision repair: an evolving picture of mitochondrial DNA repair.Bioscience reports · 2021Review
- PNKP is required for maintaining the integrity of progenitor cell populations in adult mice.Life science alliance · 2021Article
- DNA glycosylase NEIL2 functions in multiple cellular processes.Progress in biophysics and molecular biology · 2021Review
- Review
- Perturbation of base excision repair sensitizes breast cancer cells to APOBEC3 deaminase-mediated mutations.eLife · 2020Article
- NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress.eLife · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The repair of reactive oxygen species-induced base lesions and single strand breaks (SSBs) in the nuclear genome via the base excision (BER) and SSB repair (SSBR) pathways, respectively, is well characterize, and important for maintaining genomic integrity. However, the role of mitochondrial (mt) BER and SSBR proteins in mt genome maintenance is not completely clear. Here we show the presence of the oxidized base-specific DNA glycosylase Nei-like 2 (NEIL2) and the DNA end-processing enzyme polynucleotide kinase 3'-phosphatase (PNKP) in purified human mitochondrial extracts (MEs). Confocal microscopy revealed co-localization of PNKP and NEIL2 with the mitochondrion-specific protein cytochrome c oxidase subunit 2 (MT-CO2). Further, chromatin immunoprecipitation analysis showed association of NEIL2 and PNKP with the mitochondrial genes MT-CO2 and MT-CO3 (cytochrome c oxidase subunit 3); importantly, both enzymes also associated with the mitochondrion-specific DNA polymerase γ. In cell association of NEIL2 and PNKP with polymerase γ was further confirmed by proximity ligation assays. PNKP-depleted ME showed a significant decrease in both BER and SSBR activities, and PNKP was found to be the major 3'-phosphatase in human ME. Furthermore, individual depletion of NEIL2 and PNKP in human HEK293 cells caused increased levels of oxidized bases and SSBs in the mt genome, respectively. Taken together, these studies demonstrate the critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome.
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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.