Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the baker's yeast , the X- and Y'-elements are subtelomeric repetitive sequences found in all 32 and 17 telomeres, respectively. While the Y'-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear.
View Article and Find Full Text PDFSince the public long-term care insurance (LTCI) system was piloted in Chengdu, China, in October 2017, there has been considerable growth of LTC institutions in China. This study aimed to evaluate the health value effect of LTCI in older patients with severe disabilities in an LTC institution. This prospective study was based on data from 985 severe disability patients with or without LTCI from October 2017 to May 2021 in the Eighth People's Hospital, Chengdu, China.
View Article and Find Full Text PDFIn the baker's yeast Saccharomyces cerevisiae, NuA4 and SWR1-C, two multisubunit complexes, are involved in histone acetylation and chromatin remodeling, respectively. Eaf1 is the assembly platform subunit of NuA4, Swr1 is the assembly platform and catalytic subunit of SWR1-C, while Swc4, Yaf9, Arp4 and Act1 form a functional module, and is present in both NuA4 and SWR1 complexes. ACT1 and ARP4 are essential for cell survival.
View Article and Find Full Text PDFChromosomes occupy discrete spaces in the interphase cell nucleus, called chromosome territory. The structural and functional relevance of chromosome territory remains elusive. We fused chromosome 15 and 17 in mouse haploid embryonic stem cells (haESCs), resulting in distinct changes of territories in the cognate chromosomes, but with little effect on gene expression, pluripotency and gamete functions of haESCs.
View Article and Find Full Text PDFThe KEOPS complex is an evolutionarily conserved protein complex in all three domains of life (Bacteria, Archaea, and Eukarya). In budding yeast Saccharomyces cerevisiae, the KEOPS complex (ScKEOPS) consists of five subunits, which are Kae1, Bud32, Cgi121, Pcc1, and Gon7. The KEOPS complex is an ATPase and is required for tRNA N6-threonylcarbamoyladenosine modification, telomere length maintenance, and efficient DNA repair.
View Article and Find Full Text PDFPooled data from 2352 hospitalized coronavirus disease 2019 (COVID-19) patients with viral RNA in feces across 46 studies were analyzed and the pooled prevalence of fecal RNA was 46.8% (95% confidence interval [CI]: 0.383-0.
View Article and Find Full Text PDFTelomeres at the ends of eukaryotic chromosomes are essential for genome integrality and stability. In order to identify genes that sustain telomere maintenance independently of telomerase recruitment, we have exploited the phenotype of over-long telomeres in the cells that express Cdc13-Est2 fusion protein, and examined 195 strains, in which individual non-essential gene deletion causes telomere shortening. We have identified 24 genes whose deletion results in dramatic failure of Cdc13-Est2 function, including those encoding components of telomerase, Yku, KEOPS and NMD complexes, as well as quite a few whose functions are not obvious in telomerase activity regulation.
View Article and Find Full Text PDFJ Coll Physicians Surg Pak
October 2020
Objective: To investigate the incidence, clinical features, and risk factors of opportunistic infections in elderly patients with inflammatory bowel disease (IBD).
Study Design: Observational study.
Place And Duration Of Study: Department of Digestive and Geriatrics Center, Sichuan University West China Hospital, China between January 2012 and January 2019.
Background: The role of Epstein-Barr virus (EBV) in inflammatory bowel disease (IBD) remains to be elucidated. The aim of this study was to investigate the presence of EBV in the blood and intestinal mucosa of patients with IBD and evaluate the association between EBV positivity and IBD.
Methods: Patients with IBD, hospitalized between January 2015 and April 2018, were enrolled.
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.
View Article and Find Full Text PDFA nucleosome contains two copies of each histone H2A, H2B, H3 and H4. Histone H3 K4me0 and K36me3 are two key chromatin marks for de novo DNA methylation catalyzed by DNA methyltransferases in mammals. However, it remains unclear whether K4me0 and K36me3 marks on both sister histone H3s regulate de novo DNA methylation independently or cooperatively.
View Article and Find Full Text PDFKEOPS complex is one of the most conserved protein complexes in eukaryotes. It plays important roles in both telomere uncapping and tRNA N6-threonylcarbamoyladenosine (t6A) modification in budding yeast. But whether KEOPS complex plays any roles in DNA repair remains unknown.
View Article and Find Full Text PDFIt has been well documented that Tel1 positively regulates telomere-end resection by promoting Mre11-Rad50-Xrs2 (MRX) activity, while Rif2 negatively regulates telomere-end resection by inhibiting MRX activity. At uncapped telomeres, whether Tel1 or Rif2 plays any role remains largely unknown. In this work, we examined the roles of Tel1 and Rif2 at uncapped telomeres in yku70Δ and/or cdc13-1 mutant cells cultured at non-permissive temperature.
View Article and Find Full Text PDFHistone H2B lysine 123 mono-ubiquitination (H2Bub1), catalyzed by Rad6 and Bre1 in Saccharomyces cerevisiae, modulates chromatin structure and affects diverse cellular functions. H2Bub1 plays roles in telomeric silencing and telomere replication. Here, we have explored a novel role of H2Bub1 in telomere protection at uncapped telomeres in yku70Δ and cdc13-1 cells.
View Article and Find Full Text PDFEukaryotic genomes are generally organized in multiple chromosomes. Here we have created a functional single-chromosome yeast from a Saccharomyces cerevisiae haploid cell containing sixteen linear chromosomes, by successive end-to-end chromosome fusions and centromere deletions. The fusion of sixteen native linear chromosomes into a single chromosome results in marked changes to the global three-dimensional structure of the chromosome due to the loss of all centromere-associated inter-chromosomal interactions, most telomere-associated inter-chromosomal interactions and 67.
View Article and Find Full Text PDFIn Saccharomyces cerevisiae, the highly conserved Sua5 and KEOPS complex (including five subunits Kae1, Bud32, Cgi121, Pcc1 and Gon7) catalyze a universal tRNA modification, namely N-threonylcarbamoyladenosine (tA), and regulate telomere replication and recombination. However, whether telomere regulation function of Sua5 and KEOPS complex depends on the tA modification activity remains unclear. Here we show that Sua5 and KEOPS regulate telomere length in the same genetic pathway.
View Article and Find Full Text PDFHistone tail modifications can greatly influence chromatin-associated processes. Asymmetrically modified nucleosomes exist in multiple cell types, but whether modifications on both sister histones contribute equally to chromatin dynamics remains elusive. Here, we devised a bivalent nucleosome system that allowed for the constitutive assembly of asymmetrically modified sister histone H3s in nucleosomes in .
View Article and Find Full Text PDFRecent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation. CBP and p300 have been shown to catalyze multiple types of acylation but are not conserved in evolution, raising the question as to the existence of other enzymes for histone acylation and the functional relationship between well-characterized acetylation and other types of acylation. In this study, we focus on enzymes catalyzing histone crotonylation and demonstrate that among the known histone acetyltransferases, MOF, in addition to CBP and p300, also possesses histone crotonyltransferase (HCT) activity and this activity is conserved in evolution.
View Article and Find Full Text PDFRad6 and Bre1, ubiquitin-conjugating E2 and E3 enzymes respectively, are responsible for histone H2B lysine 123 mono-ubiquitination (H2Bub1) in Saccharomyces cerevisiae. Previous studies have shown that Rad6 and Bre1 regulate telomere length and recombination. However, the underlying molecular mechanism remains largely unknown.
View Article and Find Full Text PDFChronological aging of the yeast is attributed to multi-faceted traits especially those involving genome instability, and has been considered to be an aging model for post-mitotic cells in higher organisms. Telomeres are the physical ends of eukaryotic chromosomes, and are essential for genome integrity and stability. It remains elusive whether dysregulated telomerase activity affects chronological aging.
View Article and Find Full Text PDFIn the budding yeast Saccharomyces cerevisiae, heterochromatin structure is found at three chromosome regions, which are homothallic mating-type loci, rDNA regions and telomeres. To address how telomere heterochromatin is assembled under physiological conditions, we employed a de novo telomere addition system, and analyzed the dynamic chromatin changes of the TRP1 reporter gene during telomere elongation. We found that integrating a 255-bp, but not an 81-bp telomeric sequence near the TRP1 promoter could trigger Sir2 recruitment, active chromatin mark(s)' removal, chromatin compaction and TRP1 gene silencing, indicating that the length of the telomeric sequence inserted in the internal region of a chromosome is critical for determining the chromatin state at the proximal region.
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