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  • Oral presentation
  • Open Access

Role of RNH1 in the regulation of RNase H2 function

  • 1,
  • 1,
  • 1,
  • 2 and
  • 1
Pediatric Rheumatology201513(Suppl 1):O3

https://doi.org/10.1186/1546-0096-13-S1-O3

Published: 28 September 2015

Keywords

  • HeLa Cell
  • Essential Role
  • RNase Inhibitor
  • Genome Stability
  • Endogenous Level

Ribonuclease H2 plays an essential role for genome stability as it removes ribonucleotides misincorporated into genomic DNA by replicative polymerases and resolves RNA/DNA hybrids. Hypomorphic loss-of-function mutations in the genes encoding the three RNase H2 subunits cause the type I interferonopathies Aicardi-Goutières syndrome (AGS) and systemic lypus erythemotosus (SLE). We showed that in patients with AGS and SLE mutations cause enhanced levels of ribonucleotides in genomic DNA. We analyzed the proteomic environment of the RNase H2 complex and identified RNase Inhibitor 1 (RNH1) as an interactor. We validated the interaction of RNH1 with RNase H2 on an endogenous level using co-immunoprecipitation. Furthermore, we demonstrated that a siRNA-induced knockdown of RNH1 in HeLa cells causes low level DNA damage, activation of p53 and up-regulation of type I interferon-stimulated genes. These findings suggest a role of RNH1 in the regulation of RNase H2 function and implicate RNH1 in AGS pathogenesis.

Authors’ Affiliations

(1)
Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
(2)
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

Copyright

© Kind et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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