POT1
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| Location (UCSC) | Chr 7: 124.82 – 124.93 Mb | Chr 6: 25.74 – 25.81 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Protection of telomeres protein 1 is a protein that in humans is encoded by the POT1 gene.[5][6][7]
Function
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.[7]
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.[8]
Interactions
POT1 has been shown to
Pathology
- Increased transcriptional expression of this gene is associated with stomach carcinogenesisand its progression.
- Mutations in this gene have also been associated to the acquisition of the malignant features of chronic lymphocytic leukemia.[13]
- POT1 loss-of-function variants predispose to familial melanoma[14] and glioma.[15]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000128513 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029676 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 11248384.
- PMID 12391173.
- ^ a b "Entrez Gene: POT1 POT1 protection of telomeres 1 homolog (S. pombe)".
- PMID 20493859.
- S2CID 4427026.
- ^ PMID 15231715.
- ^ S2CID 11543383.
- S2CID 4370276.
- S2CID 9482133.[permanent dead link]
- PMID 24686849.
- PMID 25482530.
Further reading
- de Lange T (September 2005). "Shelterin: the protein complex that shapes and safeguards human telomeres". Genes & Development. 19 (18): 2100–10. PMID 16166375.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Loayza D, De Lange T (June 2003). "POT1 as a terminal transducer of TRF1 telomere length control". Nature. 423 (6943): 1013–8. S2CID 4370276.
- Colgin LM, Baran K, Baumann P, et al. (May 2003). "Human POT1 facilitates telomere elongation by telomerase". Current Biology. 13 (11): 942–6. S2CID 17801176.
- Loayza D, Parsons H, Donigian J, et al. (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. PMID 14715659.
- Kondo T, Oue N, Yoshida K, et al. (January 2004). "Expression of POT1 is associated with tumor stage and telomere length in gastric carcinoma". Cancer Research. 64 (2): 523–9. PMID 14744765.
- Armbruster BN, Linardic CM, Veldman T, et al. (April 2004). "Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1". Molecular and Cellular Biology. 24 (8): 3552–61. PMID 15060173.
- Liu D, Safari A, O'Connor MS, et al. (July 2004). "PTOP interacts with POT1 and regulates its localization to telomeres". Nature Cell Biology. 6 (7): 673–80. S2CID 11543383.
- Ye JZ, Hockemeyer D, Krutchinsky AN, et al. (July 2004). "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex". Genes & Development. 18 (14): 1649–54. PMID 15231715.
- 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. S2CID 21018496.
- 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. S2CID 18198999.
- Kelleher C, Kurth I, Lingner J (January 2005). "Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro". Molecular and Cellular Biology. 25 (2): 808–18. PMID 15632080.
- Yang Q, Zheng YL, Harris CC (February 2005). "POT1 and TRF2 cooperate to maintain telomeric integrity". Molecular and Cellular Biology. 25 (3): 1070–80. PMID 15657433.
- Lei M, Zaug AJ, Podell ER, et al. (May 2005). "Switching human telomerase on and off with hPOT1 protein in vitro". The Journal of Biological Chemistry. 280 (21): 20449–56. PMID 15792951.
External links
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Protection of telomeres protein 1 (POT1)
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