Efficient ligase 3-dependent microhomology-mediated end joining repair of DNA double-strand breaks in zebrafish embryos

Mutation Research
Mu-Dan HeYong-Hua Sun

Abstract

DNA double-strand break (DSB) repair is of considerable importance for genomic integrity. Homologous recombination (HR) and non-homologous end joining (NHEJ) are considered as two major mechanistically distinct pathways involved in repairing DSBs. In recent years, another DSB repair pathway, namely, microhomology-mediated end joining (MMEJ), has received increasing attention. MMEJ is generally believed to utilize an alternative mechanism to repair DSBs when NHEJ and other mechanisms fail. In this study, we utilized zebrafish as an in vivo model to study DSB repair and demonstrated that efficient MMEJ repair occurred in the zebrafish genome when DSBs were induced using TALEN (transcription activator-like effector nuclease) or CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 technologies. The wide existence of MMEJ repair events in zebrafish embryos was further demonstrated via the injection of several in vitro-designed exogenous MMEJ reporters. Interestingly, the inhibition of endogenous ligase 4 activity significantly increased MMEJ frequency, and the inhibition of ligase 3 activity severely decreased MMEJ activity. These results suggest that MMEJ in zebrafish is dependent on ligase 3 but independent of l...Continue Reading

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Citations

Apr 20, 2016·Frontiers in Genetics·Han B LeeKarl J Clark
Nov 12, 2016·Trends in Genetics : TIG·Mingyu LiWenbiao Chen
Jan 12, 2017·ACS Synthetic Biology·Zihe LiuHuimin Zhao
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Jan 29, 2019·Frontiers in Cell and Developmental Biology·Maria Luisa CayuelaMaria Caterina Mione
Dec 20, 2020·Scientific Reports·Airi IshibashiKeisuke Nimura

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