Telomeres — the protein–DNA complexes at chromosome ends — are protective devices that shield the DNA from degradation and end-to-end fusion. They comprise a telomere-capping protein, which recognizes the telomeric DNA and regulates the telomere-forming enzyme telomerase. Such capping proteins have been characterized in ciliated protozoa, but homologues in other organisms have been elusive. Reporting in Science, however, Baumann and Cech now describe a capping protein that fits telomeric DNA throughout the eukaryotic kingdom.

The authors began with a database search in the fission yeast Schizosaccharomyces pombe, and identified an open reading frame with 40% similarity at its amino terminus to the telomere-binding α-subunit from the hypotrichous ciliate Oxytricha nova. They then confirmed that this protein — called Pot1, for 'protection of telomeres' — binds specifically to single-stranded telomeric DNA. The affinity for DNA of a carboxy-terminally truncated Pot1 was an order of magnitude greater than that of the full-length protein; similar results have been obtained with the Oxytricha α-subunit, adding to the evidence that the two proteins are related in terms of function as well as sequence.

To investigate whether Pot1 is indeed involved in telomere maintenance, Baumann and Cech sporulated a heterozygous diploid pot1+/pot1− strain. The pot1− spores formed much smaller colonies than their pot1+ sisters, and DNA staining revealed that this was due to chromosomal instability — in many pot1− cells, the chromosomes had missegregated. Southern blotting of the DNA from pot1− cells showed that around 5 kb of the telomeric DNA had been lost, supporting the idea that Pot1 protects telomeric DNA.

Could there be homologous proteins in other eukaryotes? A BLAST search with the fission yeast Pot1 uncovered a human complementary DNA, which again showed highest sequence conservation near the amino terminus. Having cloned human POT1, the authors confirmed that the protein product binds human telomeric DNA. They then looked at the sequence specificity of the human and fission yeast proteins, and found that each protein binds much more strongly to its own telomeric DNA sequence.

Baumann and Cech detected messenger RNA for POT1 in all tissues examined, and they point out that this is consistent with POT1 being a housekeeping gene, “required to ensure the integrity of chromosome ends in all cells”. They note that Pot1 could also be involved in regulating the access of telomerase or other enzymes to the ends of chromosomes. But whatever its functions are finally found to be, the discovery of Pot 1 in fission yeast and humans suggests that the mechanism of telomere end protection is widely conserved.