Cell fusion studies and biochemical analysis of DNA synthesis in Werner and non-Werner cultured cells.

Abstract

Cell fusion has been used extensively to determine whether DNA synthesis can be reinitiated (“rescued”) in senescent human diploid fibroblast-like (HDFL) cells. These experiments have shown that temporary resumption of DNA synthesis can occur after fusion of senescent cells to some, but not all, continuously propagated cell lines. In contrast, fusion of senescent HDFL cells to early passage HDFL cells, never results in rescue. In this monograph, the literature describing these experiments is reviewed. In addition, we propose a model which predicts that DNA synthesis is initiated in heterokaryons between senescent HDFL cells and other cell types only when the proliferating parental cell types donate enough DNA replication factors to the common pool to exceed the threshold concentration required for initiation of DNA synthesis. Evidence is presented indicating that senescent HDFL cells cultured from patients with Werner syndrome (referred to here as Werner cells) possess an increased requirement for these replication factors. However, we will describe studies indicating that DNA polymerase alpha remains inducible following mitogen stimulation senescent cultures derived from both normal and Werner donors. Thus, senescent HDFL cells may be in a metabolic state distinct from other quiescent cell types.KeywordsSenescent CellT98G CellReplication FactorWerner SyndromeThymidine Label IndexThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.