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Dual loss of human POLQ and LIG4 abolishes random integration

Published on Dec 1, 2017in Nature Communications11.878
· DOI :10.1038/ncomms16112
Shinta Saito4
Estimated H-index: 4
(YCU: Yokohama City University),
Ryo Maeda4
Estimated H-index: 4
(Chiba University),
Noritaka Adachi29
Estimated H-index: 29
(YCU: Yokohama City University)
Sources
Abstract
Homologous recombination mediated gene targeting is highly inefficient in human cells due to random integration events, Here the authors show that dual repression of polymerase θ and DNA ligase IV eliminate random integration events.
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Single-strand annealing (SSA) is a DNA double-strand break (DSB) repair pathway that uses homologous repeats to bridge DSB ends. SSA involving repeats that flank a single DSB causes a deletion rearrangement between the repeats, and hence is relatively mutagenic. Nevertheless, this pathway is conserved, in that SSA events have been found in several organisms. In this review, we describe the mechanism of SSA and its regulation, including the cellular conditions that may favor SSA versus other DSB ...
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Abstract DNA polymerase theta (pol θ) is encoded in the genomes of many eukaryotes, though not in fungi. Pol θ is encoded by the POLQ gene in mammalian cells. The C-terminal third of the protein is a family A DNA polymerase with additional insertion elements relative to prokaryotic homologs. The N-terminal third is a helicase-like domain with DNA-dependent ATPase activity. Pol θ is important in the repair of genomic double-strand breaks (DSBs) from many sources. These include breaks formed by io...
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