DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice
Open Access
- 25 June 2013
- journal article
- review article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 41 (16), 7589-7605
- https://doi.org/10.1093/nar/gkt556
Abstract
Although the DNA double-strand break (DSB) is defined as a rupture in the double-stranded DNA molecule that can occur without chemical modification in any of the constituent building blocks, it is recognized that this form is restricted to enzyme-induced DSBs. DSBs generated by physical or chemical agents can include at the break site a spectrum of base alterations (lesions). The nature and number of such chemical alterations define the complexity of the DSB and are considered putative determinants for repair pathway choice and the probability that errors will occur during this processing. As the pathways engaged in DSB processing show distinct and frequently inherent propensities for errors, pathway choice also defines the error-levels cells opt to accept. Here, we present a classification of DSBs on the basis of increasing complexity and discuss how complexity may affect processing, as well as how it may cause lethal or carcinogenic processing errors. By critically analyzing the characteristics of DSB repair pathways, we suggest that all repair pathways can in principle remove lesions clustering at the DSB but are likely to fail when they encounter clusters of DSBs that cause a local form of chromothripsis. In the same framework, we also analyze the rational of DSB repair pathway choice.Keywords
This publication has 135 references indexed in Scilit:
- Playing the End Game: DNA Double-Strand Break Repair Pathway ChoiceMolecular Cell, 2012
- Targeting DNA damage and repair: Embracing the pharmacological era for successful cancer therapyPharmacology & Therapeutics, 2012
- Spatial Organization of the Mouse Genome and Its Role in Recurrent Chromosomal TranslocationsCell, 2012
- Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B CellsCell, 2011
- Heavy charged particle radiobiology: Using enhanced biological effectiveness and improved beam focusing to advance cancer therapyMutation Research - Reviews in Mutation Research, 2011
- Clustered DNA lesion repair in eukaryotes: Relevance to mutagenesis and cell survivalMutation Research, 2011
- Variation in base excision repair capacityMutation Research - Reviews in Mutation Research, 2011
- Delayed repair of radiation induced clustered DNA damage: Friend or foe?Mutation Research, 2011
- The fractal globule as a model of chromatin architecture in the cellChromosome Research, 2011
- Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer DevelopmentCell, 2011