Structure and mechanism of DNA polymerase β.
DNA polymerase (pol) β is a small eukaryotic DNA polymerase composed of two domains. Each domain contributes an enzymatic activity (DNA synthesis and deoxyribose phosphate lyase) during the repair of simple base lesions. These domains are termed the polymerase and lyase domains, respectively. Pol β has been an excellent model enzyme for studying the nucleotidyl transferase reaction and substrate discrimination at a molecular level. In this review, recent crystallographic studies of pol β in various liganded and conformational states during the insertion of right and wrong nucleotides as well as during the bypass of damaged DNA (apurinic sites and 8-oxoguanine) are described. Structures of these catalytic intermediates provide unexpected insights into mechanisms by which DNA polymerases enhance genome stability. These structures also provide an improved framework that permits computational studies to facilitate the interpretation of detailed kinetic analyses of this model enzyme.
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health , 111 T. W. Alexander Drive, P.O. Box 12233, MD F3-01, Research Triangle Park, North Carolina 27709, United States.
William A
WA
Beard
Samuel H
SH
Wilson
D018360:Crystallography, X-Ray; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D003854:Deoxyribonucleotides / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008274:Magnesium / Q000378:metabolism; D008956:Models, Chemical; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism; D011487:Protein Conformation
D003854:Deoxyribonucleotides; D008024:Ligands; C024829:8-hydroxyguanine; D006147:Guanine; D019951:DNA Polymerase beta; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D019761:Phosphorus-Oxygen Lyases; D008274:Magnesium