Double-Stranded Break Repair in Mammalian Cells and Precise Genome Editing

In mammalian cells, double-strand breaks (DSBs) are repaired predominantly by error-prone non-homologous end joining (NHEJ), but less prevalently by error-free template-dependent homologous recombination (HR). DSB repair pathway selection is the bedrock for genome editing. NHEJ results in random mut...

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Main Authors: Akhtar Ali, Wei Xiao, Masroor Ellahi Babar, Yanzhen Bi
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/13/5/737
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author Akhtar Ali
Wei Xiao
Masroor Ellahi Babar
Yanzhen Bi
author_facet Akhtar Ali
Wei Xiao
Masroor Ellahi Babar
Yanzhen Bi
author_sort Akhtar Ali
collection DOAJ
description In mammalian cells, double-strand breaks (DSBs) are repaired predominantly by error-prone non-homologous end joining (NHEJ), but less prevalently by error-free template-dependent homologous recombination (HR). DSB repair pathway selection is the bedrock for genome editing. NHEJ results in random mutations when repairing DSB, while HR induces high-fidelity sequence-specific variations, but with an undesirable low efficiency. In this review, we first discuss the latest insights into the action mode of NHEJ and HR in a panoramic view. We then propose the future direction of genome editing by virtue of these advancements. We suggest that by switching NHEJ to HR, full fidelity genome editing and robust gene knock-in could be enabled. We also envision that RNA molecules could be repurposed by RNA-templated DSB repair to mediate precise genetic editing.
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spelling doaj.art-3a73091809934a9d82c71f7c3a6e6c442023-11-23T11:08:41ZengMDPI AGGenes2073-44252022-04-0113573710.3390/genes13050737Double-Stranded Break Repair in Mammalian Cells and Precise Genome EditingAkhtar Ali0Wei Xiao1Masroor Ellahi Babar2Yanzhen Bi3Key Laboratory of Animal Embryo and Molecular Breeding of Hubei Province, Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, ChinaKey Laboratory of Animal Embryo and Molecular Breeding of Hubei Province, Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, ChinaThe University of Agriculture Dera Ismail Khan, Dera Ismail Khan 29220, PakistanKey Laboratory of Animal Embryo and Molecular Breeding of Hubei Province, Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, ChinaIn mammalian cells, double-strand breaks (DSBs) are repaired predominantly by error-prone non-homologous end joining (NHEJ), but less prevalently by error-free template-dependent homologous recombination (HR). DSB repair pathway selection is the bedrock for genome editing. NHEJ results in random mutations when repairing DSB, while HR induces high-fidelity sequence-specific variations, but with an undesirable low efficiency. In this review, we first discuss the latest insights into the action mode of NHEJ and HR in a panoramic view. We then propose the future direction of genome editing by virtue of these advancements. We suggest that by switching NHEJ to HR, full fidelity genome editing and robust gene knock-in could be enabled. We also envision that RNA molecules could be repurposed by RNA-templated DSB repair to mediate precise genetic editing.https://www.mdpi.com/2073-4425/13/5/737DSB repairNHEJHRRNA templategenome editing
spellingShingle Akhtar Ali
Wei Xiao
Masroor Ellahi Babar
Yanzhen Bi
Double-Stranded Break Repair in Mammalian Cells and Precise Genome Editing
Genes
DSB repair
NHEJ
HR
RNA template
genome editing
title Double-Stranded Break Repair in Mammalian Cells and Precise Genome Editing
title_full Double-Stranded Break Repair in Mammalian Cells and Precise Genome Editing
title_fullStr Double-Stranded Break Repair in Mammalian Cells and Precise Genome Editing
title_full_unstemmed Double-Stranded Break Repair in Mammalian Cells and Precise Genome Editing
title_short Double-Stranded Break Repair in Mammalian Cells and Precise Genome Editing
title_sort double stranded break repair in mammalian cells and precise genome editing
topic DSB repair
NHEJ
HR
RNA template
genome editing
url https://www.mdpi.com/2073-4425/13/5/737
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AT weixiao doublestrandedbreakrepairinmammaliancellsandprecisegenomeediting
AT masroorellahibabar doublestrandedbreakrepairinmammaliancellsandprecisegenomeediting
AT yanzhenbi doublestrandedbreakrepairinmammaliancellsandprecisegenomeediting