THEORY THAT MAY EXPLAIN THE HAYFLICK LIMIT - A MEANS TO DELETE ONE COPY OF A REPEATING SEQUENCE DURING EACH CELL-CYCLE IN CERTAIN HUMAN-CELLS SUCH AS FIBROBLASTS

A model that may explain the limited division potential of certain cel ls such as human fibroblasts in culture is presented. The central post ulate of this theory is that there exists, prior to certain key exons that code for materials needed for cell division, a unique sequence of specific repeating segments of DNA. One copy of such repeating segmen ts is deleted during each cell cycle in cells that are not protected f rom such deletion through methylation of their cytosine residues. Acco rding to this theory, the means through which such repeated sequences are removed, one per cycle, is through the sequential action of enzyme s that act much as bacterial restriction enzymes do - namely to produc e scissions in both strands of DNA in areas that correspond to the DNA base sequence recognition specificities of such enzymes. After the fi rst scission early in a replicative cycle, that enzyme becomes inhibit ed, but the cleavage of the first site exposes the closest site in the repetitive element to the action of a second restriction enzyme after which that enzyme also becomes inhibited. Then repair occurs, regener ating the original first site, Through this sequential activation and inhibition of two different restriction enzymes, only one copy of the repeating sequence is deleted during each cell cycle. In effect, the r epeating sequence operates as a precise counter of the numbers of cell doubling that have occured since the cells involved differentiated du ring development.