Abstract
Cdc13 is a single stranded telomere binding protein that specifically localizes to the telomere ends of budding yeasts and is essential for cell viability. It caps the ends of chromosomes thus preventing chromosome end-to-end fusions and exonucleolytic degradation, events that could lead to genomic instability and senescence, the hallmark of aging. Cdc13 is also involved in telomere length regulation by recruiting or preventing access of telomerase to the telomeric overhang. Recruitment of telomerase to the telomeres for G-strand extension is required for continuous cell division, while preventing its access to the telomeres through capping the chromosome ends prevents mitotic events that could lead to cell immortality, the hall mark of carcinogenesis. Cdc13 and its putative homologues human CTC1 and POT1 are therefore key to many biological processes directly associated with life extension and cancer prevention and can be viewed as an ideal target for cancer and age related therapies.
Highlights
Telomeres are short DNA repeats added to the ends of chromosomes by the reverse transcriptase telomerase [1, 2], a ribonucleoprotein enzyme that uses an integral RNA template for DNA replication [3]
Cdc13 further maintains the integrity of the chromosome ends by recruiting a number of factors, including telomerase and the DNA polymerase α, both of which are required for DNA replication [9,10,11]
It is well established that telomere elongation by telomerase takes place in late S to the G2 phase of the cell cycle [12, 13] and when the G-rich overhang is of sufficient length for proper telomerase holoenzyme assembly [14, 15]
Summary
Telomeres are short DNA repeats added to the ends of chromosomes by the reverse transcriptase telomerase [1, 2], a ribonucleoprotein enzyme that uses an integral RNA template for DNA replication [3]. One of these proteins in budding yeast is Cdc13, which associates with single stranded telomeric DNA with high affinity and specificity [4, 5]. Cdc13 further maintains the integrity of the chromosome ends by recruiting a number of factors, including telomerase and the DNA polymerase α (pol α), both of which are required for DNA replication [9,10,11].
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