rif1 supports the function of the cst complex in yeast telomere cappingrif1支持春秋国旅在酵母端粒的功能限制.pdfVIP

Rif1 Supports the Function of the CST Complex in Yeast Telomere Capping Savani Anbalagan, Diego Bonetti, Giovanna Lucchini, Maria Pia Longhese* ` Dipartimento di Biotecnologie e Bioscienze, Universita di Milano-Bicocca, Milano, Italy Abstract Telomere integrity in budding yeast depends on the CST (Cdc13-Stn1-Ten1) and shelterin-like (Rap1-Rif1-Rif2) complexes, which are thought to act independently from each other. Here we show that a specific functional interaction indeed exists among components of the two complexes. In particular, unlike RIF2 deletion, the lack of Rif1 is lethal for stn1DC cells and causes a dramatic reduction in viability of cdc13-1 and cdc13-5 mutants. This synthetic interaction between Rif1 and the CST complex occurs independently of rif1D-induced alterations in telomere length. Both cdc13-1 rif1D and cdc13-5 rif1D cells display very high amounts of telomeric single-stranded DNA and DNA damage checkpoint activation, indicating that severe defects in telomere integrity cause their loss of viability. In agreement with this hypothesis, both DNA damage checkpoint activation and lethality in cdc13 rif1D cells are partially counteracted by the lack of the Exo1 nuclease, which is involved in telomeric single-stranded DNA generation. The functional interaction between Rif1 and the CST complex is specific, because RIF1 deletion does not enhance checkpoint activation in case of CST-independent telomere capping deficiencies, such as those caused by the absence of Yku or telomerase. Thus, these data highlight a novel role for Rif1 in assisting the essential telomere protection function of the CST complex. Citation: Anbalagan S, Bonetti D, Lucchini G, Longhese MP (2011) Rif1 Supports the Function of the CST Complex in Yeast Telomere Capping. PLoS Genet 7(3): e1002024. doi:10.1371/journal.pgen.1002024 Editor: Su