Structural and functional properties of DNA polymerase delta from rabbit bone marrow.
DNA polymerase delta, the most recently described class of eukaryotic DNA polymerase, has been purified to apparent homogeneity from rabbit bone marrow. Unlike the previously known eukaryotic DNA polymerases, delta has a 3' to 5' exonuclease as an integral component of its 122 000 molecular weight, single polypeptide structure. Similar to the function with prokaryotic DNA polymerases, the 3' to 5' exonuclease assists DNA polymerase delta in maintaining the fidelity of DNA synthesis by excising misincorporated nucleotides. DNA polymerase delta and the longer known eukaryotic DNA polymerase alpha are similar in many features. Both are very sensitive to sulfhydryl inhibitors such as N-ethylmaliemide (NEM) and to the antibiotic aphidicolin. Such criteria distinguish alpha and delta from DNA polymerases beta and gamma. This has led to the conclusion that nuclear DNA replication, which is sensitive to NEM and aphidicolin, is carried out by DNA polymerase alpha. However, the similar sensitivity of delta to these reagents requires that the role of alpha and delta in nuclear DNA replication be further defined. In many features DNA polymerase delta is also similar to the viral induced DNA polymerases such as the Herpes simplex virus DNA polymerases which also have associated 3' to 5' exonuclease. Understanding of DNA synthesis and the mechanism of DNA replication fidelity in mammalian cells depends upon a further understanding of both DNA polymerases alpha and delta and the nature of the relationship they have to each other.
D000818:Animals; D016590:Aphidicolin; D001088:Arabinonucleotides / Q000494:pharmacology; D001379:Azathioprine / Q000494:pharmacology; D001853:Bone Marrow / Q000201:enzymology; D002412:Cations / Q000502:physiology; D002417:Cattle; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase / Q000302:isolation & purification* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D051379:Mice; D008970:Molecular Weight; D019384:Nucleic Acid Synthesis Inhibitors; D009711:Nucleotides / Q000494:pharmacology; D011817:Rabbits; D012294:Rifamycins / Q000494:pharmacology; D018139:Simplexvirus / Q000201:enzymology; D013045:Species Specificity; D014616:Vaccinia virus / Q000201:enzymology; D014764:Viral Proteins / Q000378:metabolism
D001088:Arabinonucleotides; D002412:Cations; D004224:Diterpenes; D019384:Nucleic Acid Synthesis Inhibitors; D009711:Nucleotides; D012294:Rifamycins; D014764:Viral Proteins; D016590:Aphidicolin; D006427:Hemin; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; D001379:Azathioprine; D005033:Ethylmaleimide