Determining if Telomeres Matter in Colon Cancer Initiation or Progression

Abstract

The nucleus of each human cell contains 46 linear chromosomes (92 ends) that are capped by thousands of repetitive TTAGGG DNA sequences (similar to the plastic tips on shoelaces). These ends, called “telomeres” have complex roles in aging and cancer and have proven to be intricately involved in such pivotal processes as the protection of genetic material, the completion of chromosome replication, the regulation of cellular aging due to progressively shortening telomeres throughout life, the initial protection against unlimited cellular growth, and, in combination with other alterations, the promotion of cancer progression. A collection of six proteins that either bind or associate with telomeres (the shelterin complex) begin to resolve a central question of how cells distinguish telomere ends from typical genomic DNA double-strand breaks (1). The consequences of telomere dysfunction are becoming more apparent by examining a growing list of human genetic diseases called telomeropathies. In certain inherited and familial cases of idiopathic pulmonary fibrosis, dyskeratosis congenita, and sporadic bone marrow failure (aplastic anemia), inheritance of short telomeres due to mutations in genes involved in the ribonucleoprotein telomerase holoenzyme lead to premature aging phenotypes (2). Telomerase is the cellular reverse transcriptase that can add TTAGGG repeats onto the telomeres and is active during early human development (3) but is silent in most adult tissues except proliferating stem cells, unless it is upregulated as part of cancer progression (4).