The induction of errors during in vitro DNA synthesis following chloroacetaldehyde-treatment of poly(dA-dT) and poly(dC-dG) templates.
Chloroacetaldehyde, a rearranged metabolic product of the human carcinogen vinyl chloride, reacts with the DNA-like polymers poly(dA-dT) and poly(dC-dG) to form etheno-adducts of the adenine and cytosine bases. These treated polymers, when used as templates for E. coli DNA polymerase I in an in vitro assay, show a decreased ability to direct DNA synthesis. At the same time, increased relative levels of non-complementary nucleotides are incorporated. With the poly(dA-dT) templates 1 dGMP residue is incorporated for every approx 60 ethenoadenine residues present whilst no increased misincorporation of dCMP was detected. With the poly(dC-dG) templates 1 misincorporation of dAMP or dTMP occurred in the presence of approx 30 and 80 ethenocytosine residues respectively. A nearest neighbour analysis shows that with the modified poly(dC-dG) templates the majority of the errors were incorporated opposite cytosine (or modified cytosine) bases.
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004256:DNA Polymerase I / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D011067:Poly dA-dT / Q000378:metabolism*; D011089:Polydeoxyribonucleotides / Q000378:metabolism*; D013698:Templates, Genetic
D011089:Polydeoxyribonucleotides; D011067:Poly dA-dT; C019530:poly(dC-dG); D004247:DNA; C004656:chloroacetaldehyde; D004256:DNA Polymerase I; D000079:Acetaldehyde