Mutagenesis by damaged deoxyribonucleotides and its prevention by MutT-type hydrolyzing enzymes.
Oxidized deoxyribonucleotides, 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP) and 8-hydroxydeoxyguanosine 5'-triphosphate (8-OH-dGTP), were introduced into Escherichia coli strains deficient in DNA polymerase IV (a Y-family DNA polymerase encoded in the dinB gene), and the MutT and Orfl35 proteins to examine their in vivo roles in mutagenesis elicited by 2-OH-dATP and 8-OH-dGTP. 2-OH-dATP elicited mutations less efficiently in the dinB- strain than in the wild type strain, suggesting involvement of DNA polymerase IV in 2-OH-dATP-induced mutations. 8-OH-dGTP and 2-OH-dATP elicited mutations more efficiently in mutT- and orfl35- strains, respectively, than those in their isogenic mutT+ and orfl35+ strains. These results indicate that these proteins play important roles in mutagenesis induced by 2-OH-dATP and 8-OH-dGTP in vivo.
Kamiya
Hiroyuki
H
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Satou
Kazuya
K
Hori
Mika
M
Iida
Emiko
E
Ishiguro
Chieko
C
Harashima
Hideyoshi
H
D000255:Adenosine Triphosphate / Q000378:metabolism*; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D016296:Mutagenesis; D011755:Pyrophosphatases / Q000378:metabolism*
D029968:Escherichia coli Proteins; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D019951:DNA Polymerase beta; D011755:Pyrophosphatases; C052211:mutT protein, E coli