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DNA double-strand break repair: From mechanistic understanding to cancer treatment
Abstract
Accurate repair of DNA double-strand breaks is essential to life. Indeed, defective DNA double-strand break repair can lead to toxicity and large scale sequence rearrangements that cause cancer and promote premature aging. Here, we highlight the two major repair systems for handling DNA double-strand breaks: homologous recombination and non-homologous end joining. To clarify recombination mechanisms, we present animations that illustrate DNA strand movements. In addition to describing how these pathways operate, we also describe why appropriate pathway choice is critical to genomic stability, and we summarize key pathway control features related to cell cycle checkpoint and apoptosis signaling. Importantly, recent progress in delineating the effects of specific defects in repair and checkpoint control has helped to explain several disease phenotypes, including cancer and premature aging. Improved understanding of these pathways has also sparked development of novel chemotherapeutic strategies that kill tumors with increased specificity and efficacy. This review aims to provide a foundational understanding of how the homologous recombination and non-homologous end joining pathways operate, and to demonstrate how a better understanding of these processes has advanced both our understanding of the underlying causes of cancer and our ability to innovate novel cancer treatment strategies.
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“In this step, RAD51 works together with BRCA2 to allow the strand invasion onto undamaged DNA duplex [119,120].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [119]
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Metadata
- Authors
- HELLEDAY, T., LO, J., VANGENT, D., & ENGELWARD, B.
- Affiliations
- Stockholm University (SE)
- Massachusetts Institute of Technology (US)
- Venue
- DNA Repair
- Publisher
- Elsevier BV
- Published
- 2007-07-01
- Volume
- 6
- Issue
- 7
- Pages
- 923-935
- ISSN
- 1568-7856 (ISSN-L)
- 1568-7864
- OpenAlex
- W2077892030
- Cited by
- 640
- References
- 132
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 9 · 2023: 10 · 2022: 22 · 2021: 23 · 2020: 32 · 2019: 29 · 2018: 22 · 2017: 22 · 2016: 36 · 2015: 42 · 2014: 52 · 2013: 60 · 2012: 53
- FWCI
- 19.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- DNA repair (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- DNA double-strand break repair, homologous recombination, non-homologous end joining, genome stability, cell cycle checkpoints, apoptosis signaling, premature aging, cancer, targeted cancer therapy
- MeSH terms
- Animals, Cell Cycle, Cell Transformation, Neoplastic, DNA Repair, DNA Replication, Humans, Neoplasms, Recombination, Genetic, Gene Rearrangement, Genomic Instability, DNA Repair Enzymes, DNA Breaks, Double-Stranded
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