RT Journal Article
SR Electronic
T1 CRISPR-induced double-strand breaks trigger recombination between homologous chromosome arms
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800267
DO 10.26508/lsa.201800267
VO 2
IS 3
A1 Erich Brunner
A1 Ryohei Yagi
A1 Marc Debrunner
A1 Dezirae Beck-Schneider
A1 Alexa Burger
A1 Eliane Escher
A1 Christian Mosimann
A1 George Hausmann
A1 Konrad Basler
YR 2019
UL https://www.life-science-alliance.org/content/2/3/e201800267.abstract
AB 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 Drosophila, 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.