Deletion of MEC1 suppresses the replicative senescence of the cdc13-2 mutant in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, telomerase recruitment to telomeres depends on a direct interaction between Cdc13, a protein that binds single-stranded telomeric DNA, and the Est1 subunit of telomerase. The cdc13-2 allele disrupts telomerase association with telomeres, resulting in progressive telomere shortening and replicative senescence. The Mec1/ATR kinase is both a positive and a negative regulator of telomerase activity and is required for the cell cycle arrest in telomerase-deficient senescent cells. In this study, we find that the deletion of MEC1 suppresses the replicative senescence of cdc13-2. This suppression is dependent on telomerase, indicating that Mec1 antagonizes telomerase-mediated telomere extension in cdc13-2 cells to promote senescence.

Actinomycosis mimicking urachal cancer / Urachustumort utánzó hasi actinomycosis

Összefoglaló. Az urachus tumorai és egyéb betegségei ritkák. A 67 éves férfi anamnézisében ismétlodo húgyúti fertozés szerepelt ciprofloxacinterápiával. Cisztoszkópia során a húgyhólyag felso részének másodlagos érintettségére utaló bullosus nyálkahártya képe mutatkozott. Az ezt követo CT-felvételek alapján az alsó medián hasfallal, húgyhólyaggal, belekkel összefüggo tumor iránydiagnózisát állították fel. A kivizsgálás során kialakuló ileus miatt Hartmann-mutétet végeztek, a tumoros jellegu elváltozás teljes és az érintett szervek részleges eltávolításával. A kórszövettani vizsgálat daganatos elváltozást nem talált, hasi, vélhetoen urachuseredetu actinomycosist igazolt: erre az eredetre a lokalizáció és a tünetek közt szereplo köldökváladékozás alapján lehetett gondolni, annak ellenére, hogy urachusmaradványt szövettanilag nem sikerült igazolni a mikroabszcedáló gyulladás által érintett szövetekben. A betegnél amoxicillinterápia indult. Átmeneti, hólyag melletti vizeletcsorgást követoen a beteg tünet- és panaszmentesen távozott a kórházból, de 13 nappal késobb a hasfali seb sterilnek véleményezett szétválása miatt ismét hospitalizálni kellett. Negatív nyomású sebkezelést követoen sikerült a hasat ismét zárni. A beteg ismét tünetmentessé vált, és fenntartott antibiotikumkezelés mellett hagyta el a kórházat. Az urachuskörnyéki tumorszeru elváltozások között az actinomycosis lehetoségét is szem elott kell tartani a differenciáldiagnosztikában. Orv Hetil. 2022; 163(4): 157-160. Summary. Tumours and other diseases of the urachus are rare. A 67-year-old male presented with a history of recurrent urinary tract infection and ciprofloxacin therapy. Cystoscopy suggested secondary involvement of the bullous upper bladder wall. The subsequent CT-based diagnosis was of a tumour infiltrating the lower median abdominal wall, the urinary bladder and bowels. Bowel obstruction developed and this led to partial resection of the involved organs along with a Hartmann's procedure. Histology revealed no neoplastic conditions, but proved abdominal actinomycosis of probable urachal origin based on the location of the tumour-like lesion and umbilical discharge among the symptoms. Urachal remnants were not identified in the perivesical tissues involved by the microabscess forming inflammation. Amoxicillin therapy was initiated. After a temporary urine leakage from the bladder, the patient became symptomless and was emitted from hospital. After 13 days, he was readmitted because of abdominal wound disruption, which was treated with negative-pressure wound therapy before the abdomen could be closed. At the time of reporting, he is still on amoxicillin, and has become symptomless again. Actinomycosis should be considered in the differential diagnosis of mass lesions of the urachal region. Orv Hetil. 2022; 163(4): 157-160.

Suppression of cdc13-2-associated senescence by pif1-m2 requires Ku-mediated telomerase recruitment.

In Saccharomyces cerevisiae, recruitment of telomerase to telomeres requires an interaction between Cdc13, which binds single-stranded telomeric DNA, and the Est1 subunit of telomerase. A second pathway involving an interaction between the yKu complex and telomerase RNA (TLC1) contributes to telomerase recruitment but cannot sufficiently recruit telomerase on its own to prevent replicative senescence when the primary Cdc13-Est1 pathway is abolished-for example, in the cdc13-2 mutant. In this study, we find that mutation of PIF1, which encodes a helicase that inhibits telomerase, suppresses the replicative senescence of cdc13-2 by increasing reliance on the yKu-TLC1 pathway for telomerase recruitment. Our findings reveal new insight into telomerase-mediated telomere maintenance.

Secondary metabolites of Hülle cells mediate protection of fungal reproductive and overwintering structures against fungivorous animals.

Fungal Hülle cells with nuclear storage and developmental backup functions are reminiscent of multipotent stem cells. In the soil, Hülle cells nurse the overwintering fruiting bodies of Aspergillus nidulans. The genome of A. nidulans harbors genes for the biosynthesis of xanthones. We show that enzymes and metabolites of this biosynthetic pathway accumulate in Hülle cells under the control of the regulatory velvet complex, which coordinates development and secondary metabolism. Deletion strains blocked in the conversion of anthraquinones to xanthones accumulate emodins and are delayed in maturation and growth of fruiting bodies. Emodin represses fruiting body and resting structure formation in other fungi. Xanthones are not required for sexual development but exert antifeedant effects on fungivorous animals such as springtails and woodlice. Our findings reveal a novel role of Hülle cells in establishing secure niches for A. nidulans by accumulating metabolites with antifeedant activity that protect reproductive structures from animal predators.

Zuo1 supports G4 structure formation and directs repair toward nucleotide excision repair.

Nucleic acids can fold into G-quadruplex (G4) structures that can fine-tune biological processes. Proteins are required to recognize G4 structures and coordinate their function. Here we identify Zuo1 as a novel G4-binding protein in vitro and in vivo. In vivo in the absence of Zuo1 fewer G4 structures form, cell growth slows and cells become UV sensitive. Subsequent experiments reveal that these cellular changes are due to reduced levels of G4 structures. Zuo1 function at G4 structures results in the recruitment of nucleotide excision repair (NER) factors, which has a positive effect on genome stability. Cells lacking functional NER, as well as Zuo1, accumulate G4 structures, which become accessible to translesion synthesis. Our results suggest a model in which Zuo1 supports NER function and regulates the choice of the DNA repair pathway nearby G4 structures.