Cannan Wendy J, Pederson David S
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont.
J Cell Physiol. 2016 Jan;231(1):3-14. doi: 10.1002/jcp.25048.
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).
由于暴露于电离辐射，所有生物体的DNA都会遭受双链断裂（DSB）。当复制叉遇到DNA损伤或修复中间体时，DSB也会形成。DSB的处理和修复会导致突变、杂合性丧失以及染色体重排，从而导致细胞死亡或癌症。后生动物中用于修复DSB的最常见途径（非同源DNA末端连接）比另一种途径（同源重组介导的修复）更易产生突变。因此，影响DSB修复途径选择的因素会影响个体的突变负担和患癌风险。本综述描述了产生DSB的放射、化学和生物学机制，并讨论了诸如DSB病因、细胞类型、细胞周期和染色质结构等变量对DSB的产生率、分布和处理的影响。最后一部分重点介绍了影响DSB产生的核小体特异性机制，以及高阶染色体卷曲与染色体破碎（染色体碎裂）之间的可能关系。
