Caenorhabditis elegans POT-1 and POT-2 Repress Telomere Maintenance Pathways

摘要

Telomeres are composed of simple tandem DNA repeats that protect the ends of linear chromosomes from replicative erosion or inappropriate DNA damage response mechanisms. The mammalian Protection Of Telomeres (POT1) protein interacts with single-stranded telomeric DNA and can exert positive and negative effects on telomere length. Of four distinct POT1 homologs in the roundworm Caenorhabditis elegans, deficiency for or resulted in progressive telomere elongation that occurred because both proteins negatively regulate telomerase. We created a POT-1::mCherry fusion protein that forms discrete foci at C. elegans telomeres, independent of , allowing for live analysis of telomere dynamics. Transgenic pot-1::mCherry repressed telomerase in mutants. Animals deficient for , but not , displayed mildly enhanced telomere erosion rates in the absence of the telomerase reverse transcriptase, . However, ; double mutants exhibited delayed senescence in comparison to animals, and senescence was further delayed in ; ; triple mutants, some of which survived robustly in the absence of telomerase. Our results indicate that and play independent roles in suppressing a telomerase-independent telomere maintenance pathway but may function together to repress telomerase.