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POT1

Wednesday 26 January 2005

The POT1 gene encodes a protein conserved across widely diverged eukaryotes that binds the G-rich strand of its own telomeric repeat sequence, consistent with a direct role in protecting chromosome ends.

Function

The human telomere binding protein hPot1 binds to the most distal single-stranded extension of telomeric DNA in vitro, and probably in vivo, as well as associating with the double-stranded telomeric DNA binding proteins TERF1 and TERF2 through the bridging proteins PTOP (also known as PIP1 or TINT1) and TIN2.

Disrupting either the DNA binding activity of hPot1 or its association with PTOP results in elongated telomeres, suggesting a role for hPot1 in telomere length regulation.

However, mutations to POT1 and Cdc13p, the fission and budding yeast genes encoding the structural orthologs of this protein, leads to telomere instability and cell death. Thus, it is possible that the hPot1 protein may also serve to cap and protect telomeres in humans.

Knocking down the expression of hPot1 in human cells causes apoptosis or senescence, as well as an increase in telomere associations and anaphase bridges, telltale signs of telomere instability.

Knockdown cells also displayed chromatin bridges between interphase cells, reminiscent of the cut phenotype that was first described in fission yeast and in which cytokinesis progresses despite a failure of chromatid separation.

hPot1 protects chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation.

See also

- telomere binding proteins
- telomeres

References

- Veldman T, Etheridge KT, Counter CM. Loss of hPot1 function leads to telomere instability and a cut-like phenotype. Curr Biol. 2004 Dec 29;14(24):2264-70. PMID: 15620654

- Baumann, P.; Cech, T. R. : Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292: 1171-1175, 2001. Note: Erratum: Science 293: 214 only, 2001. PubMed ID : 11349150

- Lei, M.; Podell, E. R.; Baumann, P.; Cech, T. R. : DNA self-recognition in the structure of Pot1 bound to telomeric single-stranded DNA. Nature 426: 198-203, 2003. PubMed ID : 14614509

- Loayza, D.; de Lange, T. : POT1 as a terminal transducer of TRF1 telomere length control. Nature 424: 1013-1018, 2003. PubMed ID : 12944955