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Cell. 2011 Apr 15;145(2):212-23. doi: 10.1016/j.cell.2011.03.005.

Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family.

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  • 1Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

Human exonuclease 1 (hExo1) plays important roles in DNA repair and recombination processes that maintain genomic integrity. It is a member of the 5' structure-specific nuclease family of exonucleases and endonucleases that includes FEN-1, XPG, and GEN1. We present structures of hExo1 in complex with a DNA substrate, followed by mutagenesis studies, and propose a common mechanism by which this nuclease family recognizes and processes diverse DNA structures. hExo1 induces a sharp bend in the DNA at nicks or gaps. Frayed 5' ends of nicked duplexes resemble flap junctions, unifying the mechanisms of endo- and exonucleolytic processing. Conformational control of a mobile region in the catalytic site suggests a mechanism for allosteric regulation by binding to protein partners. The relative arrangement of substrate binding sites in these enzymes provides an elegant solution to a complex geometrical puzzle of substrate recognition and processing.

Copyright © 2011 Elsevier Inc. All rights reserved.

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PMID:
21496642
[PubMed - indexed for MEDLINE]
PMCID:
PMC3093132
Free PMC Article

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