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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 PublicationMUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
ISSN0027-5107
Volume780Pages:86-96
AbstractDNA 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.
SubtypeArticle
KeywordDouble-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
DOI10.1016/j.mrfmmm.2015.08.004
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaBiotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
WOS SubjectBiotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
WOS KeywordGUIDED CAS9 NUCLEASE ; HOMOLOGOUS RECOMBINATION ; SACCHAROMYCES-CEREVISIAE ; VERTEBRATE CELLS ; KU80-DEFICIENT CELLS ; MAMMALIAN-CELLS ; GENE-EXPRESSION ; PATHWAY ; IV ; FISH
WOS IDWOS:000362306000010
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/27266
Collection鱼类生物学及渔业生物技术研究中心
Affiliation1.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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