4.3 Article

To indel or not to indel: Factors influencing mutagenesis during chromosomal break end joining*

期刊

DNA REPAIR
卷 118, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.dnarep.2022.103380

关键词

ATM; C-NHEJ; DNA polymerase theta; DNA-PKcs; Double -strand break repair; Gene editing

资金

  1. National Cancer Institute of the National Institutes of Health (USA) [R01CA256989, R01CA240392]

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This review describes key factors that influence the steps of DSB EJ in mammalian cells, which is significant for understanding mutagenesis resulting from clastogenic cancer therapeutics and for developing gene editing approaches.
Chromosomal DNA double-strand breaks (DSBs) are the effective lesion of radiotherapy and other clastogenic cancer therapeutics, and are also the initiating event of many approaches to gene editing. Ligation of the DSBs by end joining (EJ) pathways can restore the broken chromosome, but the repair junctions can have insertion/ deletion (indel) mutations. The indel patterns resulting from DSB EJ are likely defined by the initial structure of the DNA ends, how the ends are processed and synapsed prior to ligation, and the factors that mediate the ligation step. In this review, we describe key factors that influence these steps of DSB EJ in mammalian cells, which is significant both for understanding mutagenesis resulting from clastogenic cancer therapeutics, and for developing approaches to manipulating gene editing outcomes.

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