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Coordination of DNA single strand break repair
Open accessAbstract
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of "simple" and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks. More significant in terms of frequency are endogenous mechanisms of modification, which include hydrolytic disintegration of DNA chemical bonds, attack by reactive oxygen species and other byproducts of normal cellular metabolism, or incomplete or necessary enzymatic reactions (such as topoisomerases or repair nucleases). Both exogenous and endogenous mechanisms are associated with a high risk of single strand breakage, either produced directly or generated as intermediates of DNA repair. This review will focus upon the creation, consequences and resolution of single strand breaks, with a particular focus on two major coordinating repair proteins: poly(ADP-ribose) polymerase 1 (PARP1) and X-ray repair cross-complementing protein 1 (XRCC1).
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“DNA of mammal cells experiences over 105 modifications per day, many of which are ROS-related single-strand breaks that are detected by the DNA-break sensor poly(ADP-ribose) polymerase 1 (PARP1), and ultimately resolved by defined repair mechanisms (68).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [68]
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Metadata
- Authors
- Abbotts, R., & Wilson, D. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Wilson, David M.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 107
- Pages
- 228-244
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC5443707
- OpenAlex
- W2553815939
- Cited by
- 240
- References
- 318
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 25 · 2023: 31 · 2022: 32 · 2021: 41 · 2020: 31 · 2019: 23 · 2018: 18 · 2017: 8
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (ZIAAG000751)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- single-strand breaks, PARP1, XRCC1, DNA damage, reactive oxygen species, abasic sites, DNA cross-links, base lesions, endogenous DNA damage, meiotic recombination, class switch recombination
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, X-ray Repair Cross Complementing Protein 1, Animals, Benzopyrenes, DNA Damage, DNA Repair, Humans, Nervous System Diseases, Radiation, Ionizing, Sunlight, Reactive Oxygen Species, DNA Breaks, Single-Stranded
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