Abstract
Telomeres define the natural ends of eukaryotic chromosomes and are crucial for chromosomal stability. The budding yeast Cdc13, Stn1 and Ten1 proteins form a heterotrimeric complex, and the inactivation of any of its subunits leads to a uniformly lethal phenotype due to telomere deprotection. Although Cdc13, Stn1 and Ten1 seem to belong to an epistasis group, it remains unclear whether they function differently in telomere protection. Here, we employed the single-linear-chromosome yeast SY14, and surprisingly found that the deletion of CDC13 leads to telomere erosion and intrachromosome end-to-end fusion, which depends on Rad52 but not Yku. Interestingly, the emergence frequency of survivors in the SY14 cdc13Δ mutant was ~29 fold higher than that in either the stn1Δ or ten1Δ mutant, demonstrating a predominant role of Cdc13 in inhibiting telomere fusion. Chromosomal fusion readily occurred in the telomerase-null SY14 strain, further verifying the default role of intact telomeres in inhibiting chromosome fusion.
Highlights
Telomeres, the native ends of eukaryotic linear chromosomes, are critical for the maintenance of genome stability
A pulse-field-gel electrophoresis (PFG) analysis revealed that the single chromosome in SY14 remained intact during the passages (Figure 1—figure supplement 1)
The results showed that Rap1 was indispensable for the viability of the circular-chromosome yeast SY15 (Figure 2A), suggesting that Rap1 is essential for telomere protection and for gene transcription, consistent with a previous report that the telomere binding of Rap1 is not required for its essential functions (Alexander and Zakian, 2003)
Summary
The native ends of eukaryotic linear chromosomes, are critical for the maintenance of genome stability. They protect chromosome ends from nuclease degradation, homologous recombination, and end-to-end fusions (Bianchi and Shore, 2008; Malyavko et al, 2014; McEachern et al, 2000; Smogorzewska and de Lange, 2004; Wellinger and Zakian, 2012). Y0 elements, located immediately internal to telomeric DNA, are present in zero to four tandem copies and fall into two classes, Y0 long (6.7 kb) and Y0 short (5.2 kb). X elements, which are located centromere-proximal to telomeres or Y0 elements, are less conserved, with 8–18% divergence occurring between various X elements, and they are found in virtually all telomeres (Louis and Haber, 1991)
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