A coproofreading Zn(2+)-dependent exonuclease within a bacterial replicase.
The proofreading exonucleases of all DNA replicases contain acidic residues that chelate two Mg(2+) ions that participate in catalysis. DNA polymerase III holoenzymes contain their proofreading activity in a separate subunit, epsilon, which binds the polymerase subunit, alpha, through alpha's N-terminal php domain. Here we demonstrate that the alpha php domain contains a novel Zn(2+)-dependent 3' --> 5' exonuclease that preferentially removes mispaired nucleotides, providing the first example of a coediting nuclease.
Stano
Natalie M
NM
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Chen
Joe
J
McHenry
Charles S
CS
D002413:Cations, Divalent / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004795:Enzyme Stability; D005092:Exonucleases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D016963:Thermus thermophilus / Q000187:drug effects / Q000201:enzymology; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
D002413:Cations, Divalent; D021122:Protein Subunits; C023140:DNA replicase; D004259:DNA-Directed DNA Polymerase; D005092:Exonucleases; D015032:Zinc