Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. DNA polymerase alpha isolated from Norman murine myxosarcoma exhibited two isozyme forms, one with low specific activity and low DNA binding affinity (A1), and one with high specific activity and high DNA binding affinity (A2). 2. DNA polymerase alpha A1, but not A2, showed a significant increase in specific activity after treatment with phosphatidylinositol, ATP and phosphatidylinositol kinase, or with phosphatidylinositol-4-monophosphate. 3. Treatment of DNA polymerase alpha A1 with the phospholipase C hydrolysis product of phosphatidylinositol-4-monophosphate, inositol-1,4-bisphosphate, was sufficient to effect the transient increase in activity of polymerase A1 to a form not chromatographically distinguishable from isozyme form A2.
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PMID:Interaction of phosphatidylinositol-4-monophosphate with a low activity form of DNA polymerase alpha: a potential mechanism for enzyme activation. 254 77

DNA polymerase alpha isolated from adult-derived lymphocytes was separated into isozyme forms with low (A1) and high (A2) specific activity. In quiescent lymphocytes only A1 was detected, while mitogen-stimulated lymphocytes contained both A1 and A2 enzyme. Polymerase alpha A1, but not A2, interacted with phosphatidylinositol, ATP, and phosphatidylinositol kinase to yield an activated enzyme with increased affinity of binding to DNA. Mitogen-stimulated lymphocytes showed increased enzyme protein and total activity for both A1 and A2, but, when pre-treated with cycloheximide, exhibited an apparent increase in A2 specific activity with no increase in activity for A1 polymerase. These data suggest that mitogen stimulation of lymphocytes increased total DNA polymerase alpha activity by the phosphoinositide-related activation of polymerase alpha A1 to an A2-like form and by initiating de-novo synthesis of polymerase alpha A2.
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PMID:DNA polymerase alpha activity in mitogen-activated lymphocytes. 339 Jan 87

DNA excision repair and mitogen-initiated blastogenesis in human cells declined in efficiency as an apparent function of decreased DNA polymerase alpha specific activity with increased age of the cell donor. DNA polymerase alpha isolated from fetal cells contained a single, high-specific-activity enzyme form that could not be further activated and that was stable with regard to enzyme activity and affinity for DNA template-primer. DNA polymerase alpha isolated from adult-derived cells contained both low-specific-activity and high-specific-activity forms. The low-activity enzyme form, which showed low affinity of binding to DNA template-primer, was activated by treatment with phosphatidylinositol, 32P-ATP, and phosphatidylinositol kinase, resulting in a 32P-labeled enzyme that exhibited high affinity of binding to DNA template-primer. The activated enzyme was unstable, exhibiting a loss of 32P-label correlated with the loss of both specific activity and high affinity of binding to DNA template-primer. The data suggest that DNA polymerase alpha isolated from adult-derived human cells has low-activity and high-activity forms. Decreased specific activity of DNA polymerase alpha correlated with increased age of the donor appears to be a function of loss of an enzyme activator molecule resulting in diminished ability of the enzyme to bind DNA template-primer.
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PMID:Lability of DNA polymerase alpha correlated with decreased DNA synthesis and increased age in human cells. 348 Mar 75