Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development.

Cell | May 25, 2012

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

Mesh terms: Animals | Chromosomal Instability | DNA Replication | DNA-Directed DNA Polymerase | Embryo, Mammalian | Embryonic Stem Cells | Female | Male | Mice | Mice, Inbred C57BL | Ribonuclease H | Ribonucleotides | Tumor Suppressor Protein p53

Research resources used in this publication

None found

Research tools detected in this publication

Data used in this publication

None found

Associated grants

  • Agency: Medical Research Council, Id: MRC_MC_U127584494
  • Agency: Medical Research Council, Id: MRC_MC_U127597124
  • Agency: Medical Research Council, Id: MRC_MC_PC_U127580972
  • Agency: Medical Research Council, Id: MRC_MC_PC_U127597124
  • Agency: Medical Research Council, Id: MRC_MC_U105663140
  • Agency: Medical Research Council, Id:

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Gene Expression Omnibus

A public functional genomics data repository supporting MIAME-compliant data submissions. Tools are provided to help users query and download experiments and curated gene expression profiles. These data include 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.

tool

View all literature mentions