Modulation of dna double-strand break repair as a strategy to improve precise genome editing

Modulation of dna double-strand break repair as a strategy to improve precise genome editing

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ABSTRACT In the present day, it is possible to incorporate targeted mutations or replace a gene using genome editing techniques such as customisable CRISPR/Cas9 system. Although induction of


DNA double-strand breaks (DSBs) by genome editing tools can be repaired by both non-homologous end joining (NHEJ) and homologous recombination (HR), the skewness of the former pathway in


human and other mammals normally result in imprecise repair. Scientists working at the crossroads of DNA repair and genome editing have devised new strategies for using a specific pathway to


their advantage. Refinement in the efficiency of precise gene editing was witnessed upon downregulation of NHEJ by knockdown or using small molecule inhibitors on one hand, and upregulation


of HR proteins and addition of HR stimulators, other hand. The exploitation of cell cycle phase differences together with appropriate donor DNA length/sequence and small molecules has


provided further improvement in precise genome editing. The present article reviews the mechanisms of improving the efficiency of precise genome editing in several model organisms and in


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support SIMILAR CONTENT BEING VIEWED BY OTHERS TARGETING DOUBLE-STRAND BREAK INDEL BYPRODUCTS WITH SECONDARY GUIDE RNAS IMPROVES CAS9 HDR-MEDIATED GENOME EDITING EFFICIENCIES Article Open


access 09 May 2022 SYNERGISTIC GENE EDITING IN HUMAN IPS CELLS VIA CELL CYCLE AND DNA REPAIR MODULATION Article Open access 08 June 2020 GENOME EDITING WITH THE HDR-ENHANCING DNA-PKCS


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Dipayan Ghosh and other members of SCR laboratory for critical reading and comments on the paper. This work was supported by grants from CEFIPRA (IFC/5203-4/2015/131), DAE


(21/01/2016-BRNS/35074), DBT Glue-Grant (BT/PR23078/MED/29/1253/2017), IISc-DBT partnership programme (BT/PR27952-INF/22/212/2018) to SCR. UR is supported by Senior Research Fellowship (SRF)


from CSIR, India. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India Ujjayinee Ray & Sathees C. Raghavan


Authors * Ujjayinee Ray View author publications You can also search for this author inPubMed Google Scholar * Sathees C. Raghavan View author publications You can also search for this


author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Sathees C. Raghavan. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of


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PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ray, U., Raghavan, S.C. Modulation of DNA double-strand break repair as a strategy to improve precise genome


editing. _Oncogene_ 39, 6393–6405 (2020). https://doi.org/10.1038/s41388-020-01445-2 Download citation * Received: 06 May 2020 * Revised: 07 August 2020 * Accepted: 21 August 2020 *


Published: 03 September 2020 * Issue Date: 08 October 2020 * DOI: https://doi.org/10.1038/s41388-020-01445-2 SHARE THIS ARTICLE Anyone you share the following link with will be able to read


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