Evidence that a critical threshold of DNA polymerase-alpha activity may be required for the initiation of DNA synthesis in mammalian cell heterokaryons

J Cell Physiol. 1982 Oct;113(1):141-51. doi: 10.1002/jcp.1041130123.


The specific activity of DNA polymerase (90% alpha) was determined in nine "neoplastoid" cell lines (Martin and Sprague, 1973) and in three different strains of HDF (human diploid fibroblast-like cells), all examined in logarithmic phases of growth. This was compared to the ability of each cell type to "rescue" (reinitiate DNA synthesis in) senescent HDF cells subsequent to polyethylene glycol-mediated cell fusions. A sharp "threshold" value of DNA polymerase activity was observed below which reinitiation of DNA synthesis in heterokaryons with senescent HDF does not occur. This threshold was especially obvious when the specific activity of DNA polymerase (p moles dTTP incorporated per mg protein or per cell) was divided by the percent of S-phase cells present in each culture as determined by flow microfluorometry. Our results indicate that the specific activity of DNA polymerase-alpha (or some other factor tightly coregulated with it) in "recessive" cell types (those unable to rescue senescent cells) is only about two times this theoretical "threshold" value, and that fusion of recessive cell types to senescent HDF cells reduces the specific activity in the heterokaryon to below this minimum, thus preventing the cells from entering S phase.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle*
  • Cell Line
  • Cell Survival
  • Cell Transformation, Neoplastic
  • DNA / biosynthesis
  • DNA Replication*
  • DNA-Directed DNA Polymerase / metabolism*
  • Humans
  • Hybrid Cells / physiology*
  • Nucleic Acid Synthesis Inhibitors
  • Phenotype


  • Nucleic Acid Synthesis Inhibitors
  • DNA
  • DNA-Directed DNA Polymerase