Human POT1 Facilitates Telomere Elongation by Telomerase

AbstractMammalian telomeric DNA is mostly composed of double-stranded 5′-TTAGGG-3′ repeats and ends with a single-stranded 3′ overhang. Telomeric proteins stabilize the telomere by protecting the overhang from degradation [1, 2] or by remodeling the telomere into a T loop structure [3]. Telomerase is a ribonucleoprotein that synthesizes new telomeric DNA [4, 5]. In budding yeast, other proteins, such as Cdc13p, that may help maintain the telomere end by regulating the recruitment or local activity of telomerase have been identified [6–9]. Pot1 is a single-stranded telomeric DNA binding protein first identified in fission yeast, where it was shown to protect telomeres from degradation [10]. Human POT1 (hPOT1) protein is known to bind specifically to the G-rich telomere strand [11]. We now show that hPOT1 can act as a telomerase-dependent, positive regulator of telomere length. Three splice variants of hPOT1 were overexpressed in a telomerase-positive human cell line. All three variants lengthened telomeres, and splice variant 1 was the most effective. hPOT1 was unable to lengthen the telomeres of telomerase-negative cells unless telomerase activity was induced. These data suggest that a normal function of hPOT1 is to facilitate telomere elongation by telomerase