DNA Damage Response: Three Levels of DNA Repair Regulation
Open accessAbstract
Genome integrity is challenged by DNA damage from both endogenous and environmental sources. This damage must be repaired to allow both RNA and DNA polymerases to accurately read and duplicate the information in the genome. Multiple repair enzymes scan the DNA for problems, remove the offending damage, and restore the DNA duplex. These repair mechanisms are regulated by DNA damage response kinases including DNA-PKcs, ATM, and ATR that are activated at DNA lesions. These kinases improve the efficiency of DNA repair by phosphorylating repair proteins to modify their activities, by initiating a complex series of changes in the local chromatin structure near the damage site, and by altering the overall cellular environment to make it more conducive to repair. In this review, we focus on these three levels of regulation to illustrate how the DNA damage kinases promote efficient repair to maintain genome integrity and prevent disease.
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DDR kinases promote efficient DNA repair by directly regulating DNA repair machinery and changing the local chromatin and cellular environment.
“It was proposed recently that DDR kinases promote efficient DNA repair by directly regulating the DNA repair machinery, changing the local chromatin environment and cellular environment [166].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [166]
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Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complexPreprint
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- Authors
- Sirbu, B. M., & Cortez, D.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Cortez, D.
- ORCID
- Cortez, D.
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-06-28
- Volume
- 5
- Issue
- 8
- Pages
- a012724-a012724
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC3721278
- OpenAlex
- W2128552624
- Cited by
- 272
- References
- 149
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 17 · 2023: 15 · 2022: 22 · 2021: 25 · 2020: 32 · 2019: 30 · 2018: 12 · 2017: 23 · 2016: 25 · 2015: 19 · 2014: 20 · 2013: 7 · 2012: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- Swim Across America
- National Institutes of Health (W81XWH)
- National Cancer Institute (R01CA102729, R01CA136933)
- National Institute of Environmental Health Sciences (P30ES000267, T32ES007028)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- DNA damage response, DNA repair regulation, DNA-PKcs, ATM kinase, ATR kinase, genome stability, chromatin structure, protein phosphorylation, DNA replication fidelity
- MeSH terms
- Chromatin, DNA Damage, DNA Repair, Models, Genetic, Phosphorylation, Genomic Instability, DNA-Activated Protein Kinase, Ataxia Telangiectasia Mutated Proteins
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