Telomerase and breast cancer

Human chromosomes contain repeated TTAGGG DNA sequences at their ends (telomeres) that provide genomic stability (protect the ends from being recognized as DNA breaks needing repair) and a source of expendable DNA (a solution to the inability of the replication machinery to copy the extreme ends of chromosomes: the end replication problem) (see [1] for a review). A significant amount of truncation can occur during DNA replication without causing deleterious effects. Human telomeres progressively shorten with ongoing cell division until they reach a critical length that induces replicative senescence [2].Recent research has led to increased knowledge of the structure and function of telomeres. Telomeres end in G-rich single-stranded 3' overhangs, and can form a lariat structure called a t-loop. Telomere binding proteins such as TRF1 and TRF2 are thought to protect against nucleases and prevent DNA recombination or end joining [1]. Recent research has shown an increasing connection between DNA damage repair proteins (eg Mre11/Rad50/Nbs1, Ku, etc) and telomere biology in mammals. Double-strand break recognition and repair factors associated with the BRCA1-associated genome surveillance complex have, for instance, been linked to telomeres and telomere binding proteins [3]. BRCA1 or BRCA2 might also play a role in telomere structure and function.Although other mechanisms to maintain telomere stability are possible, the mechanism for lengthening telomeres in humans is almost always by the reactivation or upregulation of telomerase [4]. Human telomerase is a protein complex consisting of a human telomerase reverse transcriptase catalytic subunit (hTERT) that uses the human telomerase RNA component (hTR) of the complex as a template for adding TTAGGG repeats to the end of the chromosome [5,6,7]. Telomerase is only expressed in a small number of proliferating cell types, such as germ line and somatic stem cells. Most normal human cells lack telomerase activity and their telo