Telomeres and telomerase in adrenocortical carcinoma

Telomeres are the outer ends of chromosomes and consist of noncoding hexameric repeats of DNA (TTAGGG). There are two main challenges inherently connected to these structures. First, they need to be protected by special mechanisms to prevent their recognition as DNA breaks by DNA surveillance mechanisms and potential processing by the DNA repair machinery. Second, due to the semiconservative mechanism of DNA replication using RNA primers, small stretches of telomeric sequences are lost with each cell division. This is referred to as the end-replication problem. The first challenge is met by a specialized structure of the telomere and its association with protein factors that prevent its recognition as damaged DNA and regulate the access of the DNA repair machinery. In the absence of mechanisms to overcome the end-replication problem, the ongoing loss of telomere sequences in somatic cells ultimately leads to critically short and dysfunctional telomeres that will lead to signaling events, resulting in the removal of these cells from the pool of proliferating cells by mechanisms such as senescence, crisis, or potentially apoptosis. These mechanisms prevent the accumulation of telomere dysfunction-induced genomic aberrations.