Role of telomeres and telomerase in genomic instability, senescence and cancer

Abstract

Telomeres are ribonucleoprotein structures that protect the end of linear chromosomes from recognition as DNA double-stranded breaks and activation of a DNA damage response. Telomere-associated proteins also regulate telomerase, the protein responsible for maintaining telomere length. Loss of telomere function results from either alteration in the capping function at telomeres, or from progressive loss of telomeric repeats necessary to maintain proper telomeric structure. Dysfunctional telomeres activate p53 to initiate cellular senescence or apoptosis to suppress tumorigenesis. However, in the absence of p53, telomere dysfunction is an important mechanism to generate chromosomal instability commonly found in human carcinomas. Telomerase is expressed in the majority of human cancers, making it an attractive therapeutic target. Emerging anti-telomerase therapies that are currently in clinical trials might prove useful against some forms of human cancers.