Pot1 inactivation leads to rampant telomere resection and loss in one cell cycle.

Removal of the conserved telomere protein, Pot1, confers the immediate loss of fission yeast telomeres. This drastic phenotype has established the centrality of Pot1 for telomere maintenance but prohibited elucidation of the intermediate steps leading to telomere loss. To circumvent this problem, we have generated a conditional allele, pot1-1. We show that loss of Pot1 function during G1 leads to rapid telomere erosion during the ensuing S/G2 period. Precipitous telomere loss depends upon S-phase progression and is preceded by 5' telomeric resection. Telomere loss is accompanied by ATR- and Chk1-mediated checkpoint activation, but is not caused by checkpoint arrest.