Potential Roles of the Retinoblastoma Protein in Regulating Genome Editing.

Yuning Jiang,Wai Kit Chu

doi:10.3389/fcell.2018.00081

Yuning Jiang, Wai Kit Chu

Open Access

https://doi.org/10.3389/fcell.2018.00081

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Abstract

Genome editing is an important tool for modifying genomic DNA through introducing DNA insertion or deletion at specific locations of a genome. Recently CRISPR/Cas9 has been widely employed to improve the efficiency of genome editing. The Cas9 nuclease creates site-specific double strand breaks (DSBs) at targeted loci in the genome. Subsequently, the DSBs are repaired by two pathways: Homologous Recombination (HR) and Non-Homologous End-Joining (NHEJ). HR has been considered as “error-free” because it repairs DSBs by copying DNA sequences from a homologous DNA template, while NHEJ is “error-prone” as there are base deletions or insertions at the breakage site. Recently, RB1, a gene that is commonly mutated in retinoblastoma, has been reported to affect the repair efficiencies of HR and NHEJ. This review focuses on the roles of RB1 in repairing DNA DSBs, which have impacts on the precision and consequences of the genome editing, both at the targeted loci and the overall genome.

Highlights

Yuning Jiang and Wai Kit Chu*Homologous Recombination (HR) has been considered as “error-free” because it repairs double strand breaks (DSBs) by copying DNA sequences from a homologous DNA template, while NonHomologous End-Joining (NHEJ) is “error-prone” as there are base deletions or insertions at the breakage site
Genome editing is an important tool for modifying genomic DNA through introducing DNA insertion or deletion at specific locations of a genome
This review focuses on the roles of RB1 in repairing DNA double strand breaks (DSBs), which have impacts on the precision and consequences of the genome editing, both at the targeted loci and the overall genome

Summary

Yuning Jiang and Wai Kit Chu*

HR has been considered as “error-free” because it repairs DSBs by copying DNA sequences from a homologous DNA template, while NHEJ is “error-prone” as there are base deletions or insertions at the breakage site. If DSBs are created in the endogenous DNA, the homologous recombination machinery would repair the DSBs by copying the exogenous DNA By using this method, insertion or deletion of the target DNA sequence could be introduced into the desired loci. HR has been considered as “error-free” because it repairs DSBs by copying DNA sequences from a homologous DNA template, while NHEJ is “error-prone” because it can lead to small deletions or insertions at the breakage site. If no exogenous DNA is provided, repairing DSBs by NHEJ is desirable to generate deletions or insertions at the specific loci.

MECHANISMS OF DNA DSB REPAIR

Findings

RB AND THE MULTIPLE FUNCTIONS IN GENOME STABILITY