Ctp1 and the MRN-Complex Are Required for Endonucleolytic Rec12 Removal with Release of a Single Class of Oligonucleotides in Fission Yeast

DNA double-strand breaks (DSBs) are formed during meiosis by the action of the topoisomerase-like Spo11/Rec12 protein, which remains covalently bound to the 5′ ends of the broken DNA. Spo11/Rec12 removal is required for resection and initiation of strand invasion for DSB repair. It was previously shown that budding yeast Spo11, the homolog of fission yeast Rec12, is removed from DNA by endonucleolytic cleavage. The release of two Spo11 bound oligonucleotide classes, heterogeneous in length, led to the conjecture of asymmetric cleavage. In fission yeast, we found only one class of oligonucleotides bound to Rec12 ranging in length from 17 to 27 nucleotides. Ctp1, Rad50, and the nuclease activity of Rad32, the fission yeast homolog of Mre11, are required for endonucleolytic Rec12 removal. Further, we detected no Rec12 removal in a rad50S mutant. However, strains with additional loss of components localizing to the linear elements, Hop1 or Mek1, showed some Rec12 removal, a restoration depending on Ctp1 and Rad32 nuclease activity. But, deletion of hop1 or mek1 did not suppress the phenotypes of ctp1Δ and the nuclease dead mutant (rad32-D65N). We discuss what consequences for subsequent repair a single class of Rec12-oligonucleotides may have during meiotic recombination in fission yeast in comparison to two classes of Spo11-oligonucleotides in budding yeast. Furthermore, we hypothesize on the participation of Hop1 and Mek1 in Rec12 removal

Real-World Data on Topical Therapies and Annual Health Resource Utilization in Hospitalized Swiss Patients with Ulcerative Colitis.

Topical treatment with aminosalicylates and/or budesonide was shown to be highly effective in patients with ulcerative colitis (UC), while reducing the likelihood of systemic adverse effects. However, previous research has shown that topical treatment is clearly underused. We aimed to evaluate the use of topical therapy in the real-world setting. This is an observational study based on claims data of 201 Swiss adult patients who were hospitalized for UC between 2012 and 2014 and who were then followed for 1 year. A variety of factors presumably associated with topical treatment were examined. Annual health care utilization (UC-related medications, diagnostic procedures, consultations, and rehospitalizations) of patients with versus without topical therapy was compared. Of the 201 hospitalized UC patients, 82 (40.8%) were treated with topical 5-acetylsalicylic acid (ASA) and/or topical rectal steroids. The main factors significantly and positively associated with receiving topical treatment were the use of topical treatment in the year prior to the hospitalization, receiving oral 5-ASA, and living in an urban area. The mode of administration was further related to the language area. Patients with topical therapy significantly more often received other UC-related medications, such as combinations with systemic steroids. They significantly more often underwent colonoscopies and calprotectin measurements, and more often consulted a gastroenterologist in the follow-up, while there was no significant difference regarding rehospitalizations. Topical treatment is underused in patients with UC, which stands in contrast to the current European Crohn's and Colitis Organization guidelines. Patients' preferences and considerations need to be taken into account when prescribing medical therapy