The structure of the telomere end reflects its unique mode of replication. Normally, replication of a linear DNA molecule from internal origins of replication would generate to daughter molecules, each of which has one blunt end and one end with a 3' overhang after removal of the terminal RNA primer. The current model from work in budding yeast is that at the end of S-phase, telomeres undergo a processing event in which the 5' strand (sometimes called the CA strand to reflect the predominant bases in the telomere repeats) is degraded to produce a long 3' overhang (possibly 50-100 bases in yeast) which is then partially filled-in to leave a shorter 3' overhang of ~12 bases (Figure 17.1).
The removal of the RNA primer, or the action of nucleases on the repeats, causes telomeres to shorten each time the cell divides. In the absence of a mechanism to replicate the telomere repeats, the telomeres continuously shorten. In this ''mitotic clock'' hypothesis (Harley and Villeponteau, 1995), the size of the telomere repeat tract is related to the number of divisions the cell has undergone. In old cells where the telomere tract becomes too short, the cell senses this state and induces a ''short telomere checkpoint'' that causes cell cycle arrest (discussed below).
Handbook of Models for Human Aging
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