Untimely expression of gametogenic genes in vegetative cells causes uniparental disomy.
Untimely expression of gametogenic genes in vegetative cells causes uniparental disomy.
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在营养细胞中配配基因的不合时宜的表达会导致一方疾病。
DOI：
10.1038/nature21372
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发表时间：
2017-03-02
期刊：
影响因子：
64.8
通讯作者：
Grewal SI
中科院分区：
文献类型：
--
作者：
Folco HD;Chalamcharla VR;Sugiyama T;Thillainadesan G;Zofall M;Balachandran V;Dhakshnamoorthy J;Mizuguchi T;Grewal SI
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 yeastSchizosaccharomyces pombeas 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 andmmi1mutants. 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.
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DOI：
10.1083/jcb.200605074
发表时间：
2006-08-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ding DQ;Sakurai N;Katou Y;Itoh T;Shirahige K;Haraguchi T;Hiraoka Y
通讯作者：
Hiraoka Y
影响因子：
12.3
作者：
Schmidt CK;Brookes N;Uhlmann F
通讯作者：
Uhlmann F
DOI：
10.1073/pnas.232688099
发表时间：
2003-01-07
影响因子：
11.1
作者：
Hall, IM;Noma, K;Grewal, SIS
通讯作者：
Grewal, SIS
DOI：
10.1007/bf00422063
发表时间：
1986-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
NIWA, O;MATSUMOTO, T;YANAGIDA, M
通讯作者：
YANAGIDA, M
影响因子：
3.7
作者：
Chen H;Sun Y;Dong R;Yang S;Pan C;Xiang D;Miao M;Jiao B
通讯作者：
Jiao B