Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases
Open accessAbstract
Reactive oxygen species (ROS), generated endogenously during respiration or exogenously by genotoxic agents, induce oxidized bases and single-strand breaks (SSBs) in DNA that are repaired via the base excision/SSB repair (BER/SSBR) pathway in both the nucleus and mitochondria. Tightly regulated BER/SSBR with multiple sub-pathways is highly complex, and is linked to the replication and transcription. The repair-initiating DNA glycosylases (DGs) or AP-endonuclease (APE1) control the sub-pathway by stably interacting with downstream proteins usually via their common interacting domain (CID). A nonconserved CID with disordered structure usually located at one of the termini includes the sequences for covalent modifications and/or organelle targeting. While the DGs are individually dispensable, the SSBR-initiating APE1 and polynucleotide kinase 3' phosphatase (PNKP) are essential. BER/SSBR of mammalian nuclear and mitochondrial genomes share the same early enzymes. Accumulation of oxidative damage in nuclear and mitochondrial genomes has been implicated in aging and various neurological disorders. While defects in BER/SSBR proteins have been linked to hereditary neurodegenerative diseases, our recent studies implicated transition metal-induced inhibition of NEIL family DGs in sporadic diseases. This review focuses on the recent advances in repair of oxidatively damages in mammalian genomes and their linkage to aging and neurological disorders.
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Persistent oxidatively generated DNA damage and BER activity have been implicated in several human diseases, particularly cancer, inherited and acquired neurological disorders, and aging.
“However, persistent oxidatively generated DNA damage and BER activity have been implicated in several other human diseases, in particular cancer and inherited and acquired neurological disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis as well as in aging [194][195][196][197].”
From Sunlight damage to cellular DNA: focus on oxidatively generated lesions (2017) · cites this paper as [194]
Defects in DNA repair and DNA damage response pathways can lead to human diseases such as cancer and neurodegenerative diseases.
“Defective DNA repair and DDR pathways may lead to several human diseases, such as cancer and neurodegenerative diseases [6, 33–38]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [38]
Defects in DNA repair and DDR pathways are associated with cancer and neurodegenerative diseases.
“Dysfunctions in these pathways are linked to cancer and neurodegenerative diseases [6, 33–38]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [38]
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Research works printed but not linked: 2
- Liu P Qian L Sung JS de Souza-Pinto NC Zheng L Bogenhagen DF Bohr VA Wilson DM 3rd Shen B Demple B Removal of Oxidative DNA Damage via FEN1-Dependent Long-Patch Base Excision Repair in Human Cell Mitochondria Mol Cell Biol 2008b PMC2519700 18541666
- Mitra S Hegde ML Theriot CA Das A Hegde PM Hazra TK Complexity in repair of oxidative genome damage and its regulation 2009 Proceedings of Princess Takamatsu Symposium Tokyo, Japan
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- Authors
- Hegde, M. L., Mantha, A. K., Hazra, T. K., Bhakat, K. K., Mitra, S., & Szczesny, B.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Mitra, Sankar
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 133
- Issue
- 4
- Pages
- 157-168
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC3351531
- OpenAlex
- W1982187473
- Cited by
- 141
- References
- 166
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 3 · 2021: 9 · 2020: 7 · 2019: 11 · 2018: 7 · 2017: 13 · 2016: 12 · 2015: 11 · 2014: 18 · 2013: 24 · 2012: 3
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01 AG10514, P01AG010514)
- National Cancer Institute (R01 CA53791, R01 CA81063, R01CA102271, R01CA158910, R01CA081063, P01 CA92586, R01CA053791, P01CA092584)
- National Institute of Environmental Health Sciences (P30ES006676, R01ES008457, P-30-ES-06676)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- oxidative DNA damage, base excision repair, single-strand break repair, DNA glycosylase, APE1, PNKP, mitochondrial DNA repair, reactive oxygen species, aging, neurodegenerative diseases, oxidized DNA bases
- MeSH terms
- Age Factors, Aging, Animals, Central Nervous System, DNA Damage, DNA Repair, DNA, Mitochondrial, Humans, Reactive Oxygen Species, Phosphotransferases (Alcohol Group Acceptor), Oxidative Stress, Neurodegenerative Diseases, DNA-(Apurinic or Apyrimidinic Site) Lyase, DNA Glycosylases, DNA Breaks, Single-Stranded
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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