Cited by 644DNA Repair MechanismsPARP inhibition in cancer therapyDNA and Nucleic Acid Chemistry

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DNA double-strand break repair: From mechanistic understanding to cancer treatment

HELLEDAY, T, LO, J, VANGENT, D, ENGELWARD, B·2007·DNA Repair

DOI 10.1016/j.dnarep.2007.02.006

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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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Authors: HELLEDAY, T., LO, J., VANGENT, D., & ENGELWARD, B.
Affiliations: Stockholm University (SE)
Massachusetts Institute of Technology (US)
ORCID: HELLEDAY, T
LO, J
ENGELWARD, B
Venue: DNA Repair
Publisher: Elsevier BV
Published: 2007-07-01
Volume: 6
Issue: 7
Pages: 923-935
ISSN: 1568-7856 (ISSN-L)
1568-7864
DOI: 10.1016/j.dnarep.2007.02.006
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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DNA double-strand break repair: From mechanistic understanding to cancer treatment

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