Journal
CELL
Volume 163, Issue 3, Pages 759-771Publisher
CELL PRESS
DOI: 10.1016/j.cell.2015.09.038
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Funding
- intramural program of the US Department of Health and Human Services
- D.O.E. Computational Science Graduate Fellowship
- NIMH [5DP1-MH100706]
- Poitras Center Foundation
- Vallee Foundation
- Paul G. Allen Foundation
- New York Stem Cell Foundation
- Simons Foundation
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The microbial adaptive immune system CRISPR mediates defense against foreign genetic elements through two classes of RNA-guided nuclease effectors. Class 1 effectors utilize multi-protein complexes, whereas class 2 effectors rely on single-component effector proteins such as the well-characterized Cas9. Here, we report characterization of Cpf1, a putative class 2 CRISPR effector. We demonstrate that Cpf1 mediates robust DNA interference with features distinct from Cas9. Cpf1 is a single RNA-guided endonuclease lacking tracrRNA, and it utilizes a T-rich protospacer-adjacent motif. Moreover, Cpf1 cleaves DNA via a staggered DNA double-stranded break. Out of 16 Cpf1-family proteins, we identified two candidate enzymes from Acid-aminococcus and Lachnospiraceae, with efficient genome-editing activity in human cells. Identifying this mechanism of interference broadens our understanding of CRISPR-Cas systems and advances their genome editing applications.
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