Lability of DNA polymerase alpha correlated with decreased DNA synthesis and increased age in human cells

D. Busbee, V. Sylvia, J. Stec, Z. Cernosek, J. Norman

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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-acitivity 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.

Original languageEnglish (US)
Pages (from-to)1231-1239
Number of pages9
JournalJournal of the National Cancer Institute
Volume79
Issue number6
StatePublished - 1987
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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