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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Orans, J; McSweeney, EA; Iyer, RR; Hast, MA; Hellinga, HW; Modrich, P; Beese, LS

Published Date

  • April 15, 2011

Published In

Volume / Issue

  • 145 / 2

Start / End Page

  • 212 - 223

PubMed ID

  • 21496642

Pubmed Central ID

  • 21496642

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2011.03.005

Language

  • eng

Conference Location

  • United States