Efficient ligase 3-dependent microhomology-mediated end joining repair of DNA double-strand breaks in zebrafish embryos | |
He, Mu-Dan1,2; Zhang, Feng-Hua1,2; Wang, Hua-Lin1,2; Wang, Hou-Peng1; Zhu, Zuo-Yan1; Sun, Yong-Hua1 | |
2015-10-01 | |
Source Publication | MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
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ISSN | 0027-5107 |
Volume | 780Pages:86-96 |
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 ligase 4. This study will enhance our understanding of the mechanisms of MMEJ in vivo and facilitate inducing desirable mutations via DSB-induced repair. (C) 2015 Elsevier B.V. All rights reserved. |
Subtype | Article |
Keyword | Double-strand Breaks Repair Transcription Activator-like Effector Nuclease (Talen) Crispr (Clustered Regularly Interspaced Short Palindromic Repeats)/cas9 Microhomology-mediated End Joining (Mmej) Ligase 3 Ligase 4 |
DOI | 10.1016/j.mrfmmm.2015.08.004 |
WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
Indexed By | SCI |
Language | 英语 |
WOS Research Area | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology |
WOS Subject | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology |
WOS ID | WOS:000362306000010 |
WOS Keyword | GUIDED CAS9 NUCLEASE ; HOMOLOGOUS RECOMBINATION ; SACCHAROMYCES-CEREVISIAE ; VERTEBRATE CELLS ; KU80-DEFICIENT CELLS ; MAMMALIAN-CELLS ; GENE-EXPRESSION ; PATHWAY ; IV ; FISH |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ihb.ac.cn/handle/342005/27266 |
Collection | 鱼类生物学及渔业生物技术研究中心_期刊论文 |
Affiliation | 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
Recommended Citation GB/T 7714 | He, Mu-Dan,Zhang, Feng-Hua,Wang, Hua-Lin,et al. Efficient ligase 3-dependent microhomology-mediated end joining repair of DNA double-strand breaks in zebrafish embryos[J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,2015,780:86-96. |
APA | He, Mu-Dan,Zhang, Feng-Hua,Wang, Hua-Lin,Wang, Hou-Peng,Zhu, Zuo-Yan,&Sun, Yong-Hua.(2015).Efficient ligase 3-dependent microhomology-mediated end joining repair of DNA double-strand breaks in zebrafish embryos.MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,780,86-96. |
MLA | He, Mu-Dan,et al."Efficient ligase 3-dependent microhomology-mediated end joining repair of DNA double-strand breaks in zebrafish embryos".MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS 780(2015):86-96. |
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