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Title: Programmed DNA destruction by miniature CRISPR-Cas14 enzymes

Abstract

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.

Authors:
; ORCiD logo; ORCiD logo; ; ; ORCiD logo; ORCiD logo; ORCiD logo; ORCiD logo; ORCiD logo
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1482289
Grant/Contract Number:  
AC02-05CH11231; AC02–05CH11231
Resource Type:
Journal Article: Published Article
Journal Name:
Science
Additional Journal Information:
Journal Name: Science Journal Volume: 362 Journal Issue: 6416; Journal ID: ISSN 0036-8075
Publisher:
American Association for the Advancement of Science (AAAS)
Country of Publication:
United States
Language:
English

Citation Formats

Harrington, Lucas B., Burstein, David, Chen, Janice S., Paez-Espino, David, Ma, Enbo, Witte, Isaac P., Cofsky, Joshua C., Kyrpides, Nikos C., Banfield, Jillian F., and Doudna, Jennifer A. Programmed DNA destruction by miniature CRISPR-Cas14 enzymes. United States: N. p., 2018. Web. doi:10.1126/science.aav4294.
Harrington, Lucas B., Burstein, David, Chen, Janice S., Paez-Espino, David, Ma, Enbo, Witte, Isaac P., Cofsky, Joshua C., Kyrpides, Nikos C., Banfield, Jillian F., & Doudna, Jennifer A. Programmed DNA destruction by miniature CRISPR-Cas14 enzymes. United States. doi:10.1126/science.aav4294.
Harrington, Lucas B., Burstein, David, Chen, Janice S., Paez-Espino, David, Ma, Enbo, Witte, Isaac P., Cofsky, Joshua C., Kyrpides, Nikos C., Banfield, Jillian F., and Doudna, Jennifer A. Thu . "Programmed DNA destruction by miniature CRISPR-Cas14 enzymes". United States. doi:10.1126/science.aav4294.
@article{osti_1482289,
title = {Programmed DNA destruction by miniature CRISPR-Cas14 enzymes},
author = {Harrington, Lucas B. and Burstein, David and Chen, Janice S. and Paez-Espino, David and Ma, Enbo and Witte, Isaac P. and Cofsky, Joshua C. and Kyrpides, Nikos C. and Banfield, Jillian F. and Doudna, Jennifer A.},
abstractNote = {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.},
doi = {10.1126/science.aav4294},
journal = {Science},
number = 6416,
volume = 362,
place = {United States},
year = {Thu Oct 18 00:00:00 EDT 2018},
month = {Thu Oct 18 00:00:00 EDT 2018}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1126/science.aav4294

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Works referenced in this record:

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