Genome-scale CRISPR screens are efficient in non-homologous end-joining deficient cells.
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Embargo End Date
ICR Authors
Authors
Ferreira da Silva, J
Salic, S
Wiedner, M
Datlinger, P
Essletzbichler, P
Hanzl, A
Superti-Furga, G
Bock, C
Winter, G
Loizou, JI
Salic, S
Wiedner, M
Datlinger, P
Essletzbichler, P
Hanzl, A
Superti-Furga, G
Bock, C
Winter, G
Loizou, JI
Document Type
Journal Article
Date
2019-10-31
Date Accepted
2019-10-07
Abstract
The mutagenic repair of Cas9 generated breaks is thought to predominantly rely on non-homologous end-joining (NHEJ), leading to insertions and deletions within DNA that culminate in gene knock-out (KO). In this study, by taking focused as well as genome-wide approaches, we show that this pathway is dispensable for the repair of such lesions. Genetic ablation of NHEJ is fully compensated for by alternative end joining (alt-EJ), in a POLQ-dependent manner, resulting in a distinct repair signature with larger deletions that may be exploited for large-scale genome editing. Moreover, we show that cells deficient for both NHEJ and alt-EJ were still able to repair CRISPR-mediated DNA double-strand breaks, highlighting how little is yet known about the mechanisms of CRISPR-based genome editing.
Citation
Scientific Reports, 2019, 9 (1), pp. 15751 -
Source Title
Scientific Reports
Publisher
NATURE PORTFOLIO
ISSN
2045-2322
eISSN
2045-2322
Collections
Research Team
Target Val & Genome Stab