Citations 1
Repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome
Onozawa, Masahiro , Kim, Yoo Jung , Goldberg, Liat, Bergsagel, P. Leif , Kuehl, W. Michael, Aplan, Peter D. , Bergsagel, P. Leif , Zhang, Zhenhua , Varga, Tamás
Proceedings of the National Academy of Sciences | May 13, 2014 | Volume: 111 | Issue: 21 | Pages: 7729-7734
Significance We show that DNA double-strand breaks (DSBs) can be repaired by insertion of 50- to 1,000-bp sequences termed “templated-sequence insertions” (TSIs) derived from distant regions of the genome. Additional experiments indicate that the source of template for repair was primarily nuclear RNA. This mode of DNA-DSB repair by insertion is not restricted to experimentally produced breaks but also occurs at the site of spontaneous DNA DSBs in human cells. These TSIs are polymorphic in the human genome, suggesting that some TSIs occur in germ cells or embryos. Recognition of these TSIs is important in interpreting structural variations in short-read sequencing studies and provides additional polymorphic markers for population and evolution studies. This error-prone form of DNA repair may play a role in genetic diseases.