Towards a CRISPeR Understanding of Homologous Recombination with High-throughput Functional Genomics

Overview

Journal Curr Opin Genet Dev

Publisher Elsevier

Specialties Biology
Genetics

Date 2021 Sep 28

PMID 34583241

Citations 3

Authors

Samuel B Hayward

Alberto Ciccia

Affiliations

Soon will be listed here.

Abstract

CRISPR-dependent genome editing enables the study of genes and mutations on a large scale. Here we review CRISPR-based functional genomics technologies that generate gene knockouts and single nucleotide variants (SNVs) and discuss how their use has provided new important insights into the function of homologous recombination (HR) genes. In particular, we highlight discoveries from CRISPR screens that have contributed to define the response to PARP inhibition in cells deficient for the HR genes BRCA1 and BRCA2, uncover genes whose loss causes synthetic lethality in combination with BRCA1/2 deficiency, and characterize the function of BRCA1/2 SNVs of uncertain clinical significance. Further use of these approaches, combined with next-generation CRISPR-based technologies, will aid to dissect the genetic network of the HR pathway, define the impact of HR mutations on cancer etiology and treatment, and develop novel targeted therapies for HR-deficient tumors.

Citing Articles

Base-editing screens illuminate variant effects in human hematopoiesis.

Vaitsiankova A, Thakar T, Ciccia A Cell Rep Methods. 2023; 3(7):100541.

PMID: 37533644 PMC: 10391558. DOI: 10.1016/j.crmeth.2023.100541.

A genetic roadmap to the response to genotoxic agents in human cells.

Ciccia A, Greenberg R, Lees-Miller S, Nussenzweig A Fac Rev. 2022; 11:35.

PMID: 36532708 PMC: 9721265. DOI: 10.12703/r-01-0000019.

CRISPR-based genome editing through the lens of DNA repair.

Nambiar T, Baudrier L, Billon P, Ciccia A Mol Cell. 2022; 82(2):348-388.

PMID: 35063100 PMC: 8887926. DOI: 10.1016/j.molcel.2021.12.026.

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