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CRISPR-induced double-strand breaks trigger recombination between homologous chromosome arms


Brunner, Erich; Yagi, Ryohei; Debrunner, Marc; Beck-Schneider, Dezirae; Burger, Alexa; Escher, Eliane; Mosimann, Christian; Hausmann, George; Basler, Konrad (2019). CRISPR-induced double-strand breaks trigger recombination between homologous chromosome arms. Life Science Alliance, 2(3):e201800267.

Abstract

CRISPR–Cas9–based genome editing has transformed the life sciences, enabling virtually unlimited genetic manipulation of genomes: The RNA-guided Cas9 endonuclease cuts DNA at a specific target sequence and the resulting double-strand breaks are mended by one of the intrinsic cellular repair pathways. Imprecise double-strand repair will introduce random mutations such as indels or point mutations, whereas precise editing will restore or specifically edit the locus as mandated by an endogenous or exogenously provided template. Recent studies indicate that CRISPR-induced DNA cuts may also result in the exchange of genetic information between homologous chromosome arms. However, conclusive data of such recombination events in higher eukaryotes are lacking. Here, we show that in <jats:italic>Drosophila</jats:italic>, the detected Cas9-mediated editing events frequently resulted in germline-transmitted exchange of chromosome arms—often without indels. These findings demonstrate the feasibility of using the system for generating recombinants and also highlight an unforeseen risk of using CRISPR-Cas9 for therapeutic intervention.

Abstract

CRISPR–Cas9–based genome editing has transformed the life sciences, enabling virtually unlimited genetic manipulation of genomes: The RNA-guided Cas9 endonuclease cuts DNA at a specific target sequence and the resulting double-strand breaks are mended by one of the intrinsic cellular repair pathways. Imprecise double-strand repair will introduce random mutations such as indels or point mutations, whereas precise editing will restore or specifically edit the locus as mandated by an endogenous or exogenously provided template. Recent studies indicate that CRISPR-induced DNA cuts may also result in the exchange of genetic information between homologous chromosome arms. However, conclusive data of such recombination events in higher eukaryotes are lacking. Here, we show that in <jats:italic>Drosophila</jats:italic>, the detected Cas9-mediated editing events frequently resulted in germline-transmitted exchange of chromosome arms—often without indels. These findings demonstrate the feasibility of using the system for generating recombinants and also highlight an unforeseen risk of using CRISPR-Cas9 for therapeutic intervention.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 June 2019
Deposited On:18 Feb 2020 10:06
Last Modified:01 Mar 2020 14:52
Publisher:Life Science Alliance
ISSN:2575-1077
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.26508/lsa.201800267
PubMed ID:31196871
Project Information:
  • : FunderSNSF
  • : Grant ID310030B_173331
  • : Project TitleTCF and Ã�-catenin independent outputs of Wingless/Wnt signaling
  • : FunderSNSF
  • : Grant IDPP00P3_170623
  • : Project TitleDeciphering the control of lateral mesoderm cell fates in zebrafish (extension)
  • : FunderSNSF
  • : Grant ID31003A_182532
  • : Project TitleA Systems Approach to Size Control in Drosophila
  • : FunderSNSF
  • : Grant ID31003A_162557
  • : Project TitleA Systems Approach to Size Control in Drosophila

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