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The presence of ribonucleotides in genomic DNA is undesirable given their increased susceptibility to hydrolysis. Ribonuclease (RNase) H enzymes that recognize and process such embedded ribonucleotides are present in all domains of life. However, in unicellular organisms such as budding yeast, they are not required for viability or even efficient cellular proliferation, while in humans, RNase H2 hypomorphic mutations cause the neuroinflammatory disorder Aicardi-Goutières syndrome. Here, we report that RNase H2 is an essential enzyme in mice, required for embryonic growth from gastrulation onward. RNase H2 null embryos accumulate large numbers of single (or di-) ribonucleotides embedded in their genomic DNA (>1,000,000 per cell), resulting in genome instability and a p53-dependent DNA-damage response. Our findings establish RNase H2 as a key mammalian genome surveillance enzyme required for ribonucleotide removal and demonstrate that ribonucleotides are the most commonly occurring endogenous nucleotide base lesion in replicating cells.
Pubmed ID: 22579044 RIS Download
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Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsAn Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsCenter that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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