Telomore dysfunction and cancer

Abstract

Unlike the circular structure of prokaryotic chromosome, the structure of eukaryotic chromosomes is linear. To prevent the ends of linear chromosomes from being recognized as double-stranded DNA breaks by DNA damage, chromosome end is capped by the special chromatin structure, telomere. Telomere in vertebrate consists of TTAGGG tandem repeats and telosome/shelterin complex including TRF1, TRF2, RAP1, TIN2, TPP1, and POT1. The average length of human telomere is 10∼15 kb at birth, and several rounds of cell division lead to telomere shortening in somatic cells due to the absence of telomerase, a reverse transcriptase, adding TTAGGG repeats at chromosome ends. The uncapping telomere by telomere attrition causes genomic instability activating cell cycle checkpoints and inducing cell cycle arrest, senescence, or apoptosis. Highly-proliferative tumor cells that have the impaired checkpoints and short telomeres can escape normal limits on cell proliferation, resulting in massive genome instability and malignancy of tumor cells. In this review, we provide an overview of telomere structure and function, and the relationship between telomere dysfunction and the initiation of human cancer