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Title: Programmed DNA destruction by miniature CRISPR-Cas14 enzymes

CRISPR-Cas systems provide microbes with adaptive immunity to infectious nucleic acids and are widely employed as genome editing tools. These tools use RNA-guided Cas proteins whose large size (950 to 1400 amino acids) has been considered essential to their specific DNA- or RNA-targeting activities. Here we present a set of CRISPR-Cas systems from uncultivated archaea that contain Cas14, a family of exceptionally compact RNA-guided nucleases (400 to 700 amino acids). Despite their small size, Cas14 proteins are capable of targeted single-stranded DNA (ssDNA) cleavage without restrictive sequence requirements. Moreover, target recognition by Cas14 triggers nonspecific cutting of ssDNA molecules, an activity that enables high-fidelity single-nucleotide polymorphism genotyping (Cas14-DETECTR). Metagenomic data show that multiple CRISPR-Cas14 systems evolved independently and suggest a potential evolutionary origin of single-effector CRISPR-based adaptive immunity.

 
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NSF-PAR ID:
10079628
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Publisher / Repository:
American Association for the Advancement of Science (AAAS)
Date Published:
Journal Name:
Science
Volume:
362
Issue:
6416
ISSN:
0036-8075
Page Range / eLocation ID:
p. 839-842
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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