Abstract

A theory of marginotomy has been proposed to explain the limitation of the cell doubling potential of clones of normal somatic cells. Marginotomy of DNA is the shortening of the replica with respect to the template. Two possible mechanisms of marginotomy are discussed. The first mechanism is a DNA-polymerase, postulated to have a catalytically inactive zone lying between the catalytic centre and the outer edge of the enzyme molecule. The terminal template segment which is equal to the length of the non-catalytic marginal zone of the DNA-polymerase will not appear in the replica. The second mechanism of marginotomy results from a requirement for an initiating RNA-primer for activity of some DNA-polymerases. In this case the final DNA replica will be shorter than the template by the length of RNA-primer.

Marginotomy causes the appearance, in the daughters of dividing cells, of more and more shortened end-genes, the so-called telogenes, with every new mitosis. The telogenes function as the starting points of end-replicons in chromosomes and also as "buffers", being sacrificed during successive mitoses. After the exhaustion of telogenes the cells become aged and are eliminated due to the loss of some vitally important genes localized in end-replicons. Marginotomy is therefore responsible for the loss with age of various cell clones of the body, including some endocrine cell clones. Therefore marginotomy may be the primary cause of various disorders of age of the ageing of multicellular organisms.