RRC ID 47499
著者 Folco HD, Chalamcharla VR, Sugiyama T, Thillainadesan G, Zofall M, Balachandran V, Dhakshnamoorthy J, Mizuguchi T, Grewal SI.
タイトル Untimely expression of gametogenic genes in vegetative cells causes uniparental disomy.
ジャーナル Nature
Abstract Uniparental disomy (UPD), in which an individual contains a pair of homologous chromosomes originating from only one parent, is a frequent phenomenon that is linked to congenital disorders and various cancers. UPD is thought to result mostly from pre- or post-zygotic chromosome missegregation. However, the factors that drive UPD remain unknown. Here we use the fission yeast Schizosaccharomyces pombe as a model to investigate UPD, and show that defects in the RNA interference (RNAi) machinery or in the YTH domain-containing RNA elimination factor Mmi1 cause high levels of UPD in vegetative diploid cells. This phenomenon is not due to defects in heterochromatin assembly at centromeres. Notably, in cells lacking RNAi components or Mmi1, UPD is associated with the untimely expression of gametogenic genes. Deletion of the upregulated gene encoding the meiotic cohesin Rec8 or the cyclin Crs1 suppresses UPD in both RNAi and mmi1 mutants. Moreover, overexpression of Rec8 is sufficient to trigger UPD in wild-type cells. Rec8 expressed in vegetative cells localizes to chromosomal arms and to the centromere core, where it is required for localization of the cohesin subunit Psc3. The centromeric localization of Rec8 and Psc3 promotes UPD by uniquely affecting chromosome segregation, causing a reductional segregation of one homologue. Together, these findings establish the untimely vegetative expression of gametogenic genes as a causative factor of UPD, and provide a solid foundation for understanding this phenomenon, which is linked to diverse human diseases.
巻・号 543(7643)
ページ 126-130
公開日 2017-3-2
DOI 10.1038/nature21372
PII nature21372
PMID 28199302
PMC PMC5567995
MeSH Centromere / metabolism Chromosomal Proteins, Non-Histone / metabolism Chromosome Segregation / genetics Cyclins / deficiency Cyclins / genetics Diploidy Gene Expression Regulation, Fungal* Germ Cells / metabolism* Heterochromatin / metabolism Humans Meiosis / genetics Models, Biological* Mutation* Phosphoproteins / deficiency Phosphoproteins / genetics Phosphoproteins / metabolism RNA Interference Schizosaccharomyces / cytology* Schizosaccharomyces / genetics* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism Time Factors Uniparental Disomy / genetics* Uniparental Disomy / pathology mRNA Cleavage and Polyadenylation Factors / deficiency mRNA Cleavage and Polyadenylation Factors / genetics mRNA Cleavage and Polyadenylation Factors / metabolism
IF 42.779
引用数 16
WOS 分野 CELL BIOLOGY
リソース情報
酵母 FY23680(SP44)