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Genome instability consequences of RNase H2 Aicardi-Goutières syndrome alleles.
DNA Repair ( IF 3.8 ) Pub Date : 2019-04-04 , DOI: 10.1016/j.dnarep.2019.04.002
Catherine J Potenski 1 , Anastasiya Epshtein 1 , Christopher Bianco 2 , Hannah L Klein 1
Affiliation  

The RNase H2 complex is a conserved heterotrimeric enzyme that degrades RNA:DNA hybrids and promotes excision of rNMPs misincorporated during DNA replication. Failure to remove ribonucleotides from DNA leads to genomic instability in yeast and humans. The monogenic Aicardi-Goutières syndrome (AGS) results from mutation in one of several genes, among which are those encoding the RNase H2 subunits. The complete cellular and genomic consequences of RNASEH2 mutations and the precise connection to disease remain unclear. To learn more about the effect of RNASEH2 mutations on the cell, we used yeast as a model of AGS disease. We have generated yeast strains bearing AGS-associated mutations in RNASEH2 genes. There is a range of disease presentation in patients bearing these RNASEH2 variants. Here we report on in vivo phenotypes of genomic instability, including mutation and recombination rates, and synthetic gene interactions. These phenotypes provide insight into molecular consequences of RNASEH2 mutations, and lay the groundwork for further study of genomic instability as a contributing factor to AGS disease.

中文翻译:

RNase H2心律失常综合征等位基因的基因组不稳定性后果。

RNase H2复合物是一种保守的异三聚体酶,可降解RNA:DNA杂种并促进DNA复制过程中掺入错误的rNMP的切除。无法从DNA中去除核糖核苷酸会导致酵母和人类的基因组不稳定。单基因的Aicardi-Goutières综合征(AGS)是由几个基因之一的突变导致的,其中一些基因编码RNase H2亚基。RNASEH2突变的完整细胞和基因组后果以及与疾病的确切联系尚不清楚。要了解有关RNASEH2突变对细胞的影响的更多信息,我们使用了酵母作为AGS疾病的模型。我们已经产生了在RNASEH2基因中带有AGS相关突变的酵母菌株。携带这些RNASEH2变异的患者有多种疾病表现。在这里,我们报道了基因组不稳定性的体内表型,包括突变和重组率,以及合成基因相互作用。这些表型提供了对RNASEH2突变的分子后果的认识,并为进一步研究基因组不稳定性作为AGS疾病的成因奠定了基础。
更新日期:2019-11-18
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