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In S. cerevisiae, mutations in genes that encode telomerase components, such as the genes EST1, EST2, EST3, and TLC1, result in the loss of telomerase activity in vivo. Two telomerase-independent mechanisms can overcome the resulting senescence. Type I survival is characterized by amplification of the subtelomeric Y' elements with a short telomere repeat tract at the terminus. Type II survivors arise through the abrupt addition of long tracts of telomere repeats. Both mechanisms are dependent on RAD52 and on either RAD50 or RAD51. We show here that the telomere elongation pathway in yeast (type II) is dependent on SGS1, the yeast homolog of the gene products of Werner's (WRN) and Bloom's (BLM) syndromes. Survival in the absence of SGS1 and EST2 is dependent upon RAD52 and RAD51 but not RAD50. We propose that the RecQ family helicases are required for processing a DNA structure specific to eroding telomeres.

BackgroundLittle is known about patients with severe symptomatic aortic stenosis (AS) who receive medical management despite evaluation at a heart valve treatment center.ObjectiveWe identified patient characteristics associated with medical management, physician-reported reasons for selecting medical management, and patients’ perceptions of their involvement and satisfaction with treatment selection.Methods and resultsOf 454 patients evaluated for AS at 9 established heart valve treatment centers from December 12, 2013 to August 19, 2014, we included 407 with severe symptomatic AS. Information was collected using medical record review and survey of patients and treating physicians. Of 407 patients, 212 received transcatheter aortic valve replacement (TAVR), 124 received surgical aortic valve replacement (SAVR), and 71 received medical management (no SAVR/TAVR). Thirty-day predicted mortality was higher in patients receiving TAVR (8.7%) or medical management (9.8%) compared with SAVR (3.4%) (P<0.001). Physician-reported reasons for medical management included patient preference (31.0%), medical futility (19.7%), inoperability/anatomic infeasibility (11.3%), and inadequate vascular access (8.5%). Compared with patients receiving AVR, medically managed patients were less likely to report that they received enough information about the pros and cons of treatment options (P = 0.03), that their physicians involved them in treatment decisions (P<0.001), and that final decisions were the right ones (P<0.001).ConclusionsPatient preference was the most common physician-reported reason for selecting non-invasive AS management, yet patients not undergoing AVR after valve center evaluation reported being less likely to receive sufficient education about treatment options and more likely to feel uncertain about final treatment decisions. Greater attention to shared decision making may improve the experience of care for this vulnerable group of patients.

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