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Repair of Endogenous DNA Damage
Abstract
The remarkable stability of genes seemed a puzzlingfeature in the early days of molecular biology. It was evensuggested that new laws of physics might emerge to explain biological paradigms such as the resilience of thegenetic information. The complementary sequences inthe DNA double-helical structure provided a partial answer as to how this stability is retained, but it still tookmore than 10 years after the Watson and Crick 1953model to realize that radiation-damaged residues in DNAcould be corrected by a local excision-repair process. Inretrospect, the early concerns were fully justified; mammalian cellular DNA is a constant target of thermal"noise" in the form of spontaneous hydrolysis at 37ºC,and it is also susceptible to damage caused by active oxygen as well as reactive metabolites and coenzymes. Theresulting lesions are generally removed by the base excision repair (BER) pathway, resulting in short replacementpatches within one of the two DNA strands. Consequently, nonreplicating DNA is not absolutely stable butturns over at a relevant, albeit slow, rate in vivo. This endogenous repair is sufficiently accurate and efficient toexplain the apparent stability of the genetic material...
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“the majority ultimately manifest in the form of single‐strand breaks (SSBs)”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Lindahl & Barnes, 2000
In the citing paper
“reactive oxygen species (ROS), which attack DNA to form oxidized bases and abasic sites”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Lindahl & Barnes, 2000
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Metadata
- Authors
- LINDAHL, T., & BARNES, D. E.
- ORCID
- LINDAHL, T.
- Venue
- Cold Spring Harbor Symposia on Quantitative Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-01-01
- Volume
- 65
- Issue
- 0
- Pages
- 127-134
- ISSN
- 0091-7451 (ISSN-L)
- 1943-4456
- OpenAlex
- W2010677667
- Cited by
- 714
- References
- 60
- Citations by year
- 2026: 22 · 2025: 33 · 2024: 44 · 2023: 41 · 2022: 57 · 2021: 94 · 2020: 57 · 2019: 45 · 2018: 37 · 2017: 52 · 2016: 39 · 2015: 23 · 2014: 37 · 2013: 26 · 2012: 28
- Type
- posted content
- Language
- en
- Open access
- closed
- Locations
- Cold Spring Harbor Symposia on Quantitative Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (F31CA260794)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- DNA repair, endogenous DNA damage, base excision repair, spontaneous hydrolysis, reactive oxygen species, DNA stability, excision repair
- MeSH terms
- Animals, DNA, DNA Damage, DNA Repair, N-Glycosyl Hydrolases, Mice, Knockout, DNA-Formamidopyrimidine Glycosylase, DNA Glycosylases, Mice, Uracil-DNA Glycosidase
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