This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex known as shelterin, that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Alternatively spliced transcript variants have been described.
The absence of POT1 in mouse embryonic fibroblasts and chicken cells leads to a detrimental DNA damage response on telomeres resulting in telomere dysfunction-induced foci (TIFs). POT1 is required for telomere protection because it allows for telomere inhibition of DNA damage response factors. The protein also serves a role in the regulation of telomerase activity on telomeres. In vitro experiments utilizing human POT1 have shown that reduction in POT1 levels result in the elongation of telomeres.
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Loayza D, Parsons H, Donigian J, Hoke K, de Lange T (March 2004). "DNA binding features of human POT1: a nonamer 5'-TAGGGTTAG-3' minimal binding site, sequence specificity, and internal binding to multimeric sites". The Journal of Biological Chemistry. 279 (13): 13241–8. doi:10.1074/jbc.M312309200. PMID14715659.
Kondo T, Oue N, Yoshida K, Mitani Y, Naka K, Nakayama H, Yasui W (January 2004). "Expression of POT1 is associated with tumor stage and telomere length in gastric carcinoma". Cancer Research. 64 (2): 523–9. doi:10.1158/0008-5472.CAN-03-1196. PMID14744765.
Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (July 2004). "PTOP interacts with POT1 and regulates its localization to telomeres". Nature Cell Biology. 6 (7): 673–80. doi:10.1038/ncb1142. PMID15181449.
Lei M, Podell ER, Cech TR (December 2004). "Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection". Nature Structural & Molecular Biology. 11 (12): 1223–9. doi:10.1038/nsmb867. PMID15558049.
Veldman T, Etheridge KT, Counter CM (December 2004). "Loss of hPot1 function leads to telomere instability and a cut-like phenotype". Current Biology. 14 (24): 2264–70. doi:10.1016/j.cub.2004.12.031. PMID15620654.
Lei M, Zaug AJ, Podell ER, Cech TR (May 2005). "Switching human telomerase on and off with hPOT1 protein in vitro". The Journal of Biological Chemistry. 280 (21): 20449–56. doi:10.1074/jbc.M502212200. PMID15792951.