Mechanisms and Consequences of Double‐Strand DNA Break Formation in Chromatin

2015/06/03 by Wendy J. Cannan, David S. Pederson · 491 citations
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · #Biology #Carcinogens and Genotoxicity Assessment #Cell biology #Chromatin #Chromothripsis #DNA #DNA Repair Mechanisms #DNA damage #DNA repair #Genetics #Genome instability #Homologous recombination #Plant Genetic and Mutation Studies

paper · open access · doi:10.1002/jcp.25048

published in Journal of Cellular Physiology 231(1), 3-14 (Wiley)

openalex publication_date 2015/06/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

All organisms suffer double-strand breaks (DSBs) in their DNA as a result of exposure to ionizing radiation. DSBs can also form when replication forks encounter DNA lesions or repair intermediates. The processing and repair of DSBs can lead to mutations, loss of heterozygosity, and chromosome rearrangements that result in cell death or cancer. The most common pathway used to repair DSBs in metazoans (non-homologous DNA end joining) is more commonly mutagenic than the alternative pathway (homologous recombination mediated repair). Thus, factors that influence the choice of pathways used DSB repair can affect an individual's mutation burden and risk of cancer. This review describes radiological, chemical, and biological mechanisms that generate DSBs, and discusses the impact of such variables as DSB etiology, cell type, cell cycle, and chromatin structure on the yield, distribution, and processing of DSBs. The final section focuses on nucleosome-specific mechanisms that influence DSB production, and the possible relationship between higher order chromosome coiling and chromosome shattering (chromothripsis).

Citations

• Über einen die Erzeugung und Verwandlung des Lichtes betreffenden heuristischen Gesichtspunkt

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