Cited by 141DNA Repair MechanismsGenetics, Aging, and Longevity in Model OrganismsMitochondrial Function and Pathology

Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases

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Hegde, Muralidhar L., Mantha, Anil K., Hazra, Tapas K., Bhakat, Kishor K., Mitra, Sankar, Szczesny, Bartosz·2012·Mechanisms of Ageing and Development

Abstract

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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Crossref · 10.1016/j.mad.2012.01.005

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Research works printed but not linked: 2

  1. 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
  2. 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)
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
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

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