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The Pif1 Helicase, a Negative Regulator of Telomerase, Acts Preferentially at Long Telomeres


Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The baker’s yeast Pif1 DNA helicase inhibits both telomerase-mediated lengthening of existing telomeres and the formation of new telomeres at double strand breaks. By virtue of its ATPase activity, Pif1 reduces the level of telomerase binding to telomeres. Here, we report that the association of the telomerase subunits Est2 and Est1 at a DNA break was increased in the absence of Pif1, suggesting that Pif1 affects telomere length and new telomere formation by similar mechanisms. In cells lacking Pif1, Est2 and Est1 no longer bound preferentially to short telomeres, a larger fraction of telomeres was lengthened and the amount of telomeric DNA added per telomere was increased compared to wild type cells. Furthermore, by two different assays, Pif1 bound preferentially to long telomeres in vivo. Thus, preferential lengthening of short telomeres is achieved in part by targeting Pif1, a negative regulator of telomerase, to long telomeres.


Vyšlo v časopise: The Pif1 Helicase, a Negative Regulator of Telomerase, Acts Preferentially at Long Telomeres. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005186
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005186

Souhrn

Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The baker’s yeast Pif1 DNA helicase inhibits both telomerase-mediated lengthening of existing telomeres and the formation of new telomeres at double strand breaks. By virtue of its ATPase activity, Pif1 reduces the level of telomerase binding to telomeres. Here, we report that the association of the telomerase subunits Est2 and Est1 at a DNA break was increased in the absence of Pif1, suggesting that Pif1 affects telomere length and new telomere formation by similar mechanisms. In cells lacking Pif1, Est2 and Est1 no longer bound preferentially to short telomeres, a larger fraction of telomeres was lengthened and the amount of telomeric DNA added per telomere was increased compared to wild type cells. Furthermore, by two different assays, Pif1 bound preferentially to long telomeres in vivo. Thus, preferential lengthening of short telomeres is achieved in part by targeting Pif1, a negative regulator of telomerase, to long telomeres.


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