Journal
CELL
Volume 145, Issue 2, Pages 212-223Publisher
CELL PRESS
DOI: 10.1016/j.cell.2011.03.005
Keywords
-
Categories
Funding
- National Institutes of Health [R01 GM091487, R01 GM45190, P01 CA092584]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
- DOE with the U.S. Department of Energy [DE-AC02-05CH11231]
Ask authors/readers for more resources
Human exonuclease 1 (hExo1) plays important roles in DNA repair and recombination processes that maintain genomic integrity. It is a member of the 50 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 50 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available