Activation of a low specific activity form of DNA polymerase alpha by inositol-1,4-bisphosphate.
A low activity form of DNA polymerase alpha immunoaffinity-purified from adult-derived human fibroblasts was activated by interaction with phosphatidylinositol-4-monophosphate, while a high activity form of the enzyme did not interact with phosphatidylinositol-4-monophosphate or its derivatives. Phosphatidylinositol-4-monophosphate was apparently hydrolyzed in the presence of a highly purified low activity form of DNA polymerase alpha, effecting the release of diacylglycerol and the retention of inositol-1,4-bisphosphate by the enzyme complex. The resulting inositol-1,4-bisphosphate/protein complex exhibited increased affinity of binding to DNA template/primer and increased deoxynucleotidyltransferase activity. These data indicate that inositol-1,4-bisphosphate may function as an effector molecule in the activation of a low activity form of human DNA polymerase alpha and suggest that it may function as a second messenger during the initiation of mitosis in stimulated cells.
Sylvia
V
V
Department of Anatomy, Texas A & M University, College Station 77843.
Curtin
G
G
Norman
J
J
Stec
J
J
Busbee
D
D
D019870:1-Phosphatidylinositol 4-Kinase; D002478:Cells, Cultured; D004257:DNA Polymerase II / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology*; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D010770:Phosphotransferases / Q000378:metabolism; D013403:Sugar Phosphates / Q000494:pharmacology*
D007295:Inositol Phosphates; D007527:Isoenzymes; D013403:Sugar Phosphates; C044259:inositol 1,4-bis(phosphate); D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D004257:DNA Polymerase II