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Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex.
Nucleic Acids Res 2009; 37(1):96-110NA

Abstract

Eukaryotic RNase H2 is a heterotrimeric enzyme. Here, we show that the biochemical composition and stoichiometry of the human RNase H2 complex is consistent with the properties previously deduced from genetic studies. The catalytic subunit of eukaryotic RNase H2, RNASEH2A, is well conserved and similar to the monomeric prokaryotic RNase HII. In contrast, the RNASEH2B and RNASEH2C subunits from human and Saccharomyces cerevisiae share very little homology, although they both form soluble B/C complexes that may serve as a nucleation site for the addition of RNASEH2A to form an active RNase H2, or for interactions with other proteins to support different functions. The RNASEH2B subunit has a PIP-box and confers PCNA binding to human RNase H2. Unlike Escherichia coli RNase HII, eukaryotic RNase H2 acts processively and hydrolyzes a variety of RNA/DNA hybrids with similar efficiencies, suggesting multiple cellular substrates. Moreover, of five analyzed mutations in human RNASEH2B and RNASEH2C linked to Aicardi-Goutières Syndrome (AGS), only one, R69W in the RNASEH2C protein, exhibits a significant reduction in specific activity, revealing a role for the C subunit in enzymatic activity. Near-normal activity of four AGS-related mutant enzymes was unexpected in light of their predicted impairment causing the AGS phenotype.

Authors+Show Affiliations

Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

19015152

Citation

Chon, Hyongi, et al. "Contributions of the Two Accessory Subunits, RNASEH2B and RNASEH2C, to the Activity and Properties of the Human RNase H2 Complex." Nucleic Acids Research, vol. 37, no. 1, 2009, pp. 96-110.
Chon H, Vassilev A, DePamphilis ML, et al. Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. Nucleic Acids Res. 2009;37(1):96-110.
Chon, H., Vassilev, A., DePamphilis, M. L., Zhao, Y., Zhang, J., Burgers, P. M., ... Cerritelli, S. M. (2009). Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. Nucleic Acids Research, 37(1), pp. 96-110. doi:10.1093/nar/gkn913.
Chon H, et al. Contributions of the Two Accessory Subunits, RNASEH2B and RNASEH2C, to the Activity and Properties of the Human RNase H2 Complex. Nucleic Acids Res. 2009;37(1):96-110. PubMed PMID: 19015152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. AU - Chon,Hyongi, AU - Vassilev,Alex, AU - DePamphilis,Melvin L, AU - Zhao,Yingming, AU - Zhang,Junmei, AU - Burgers,Peter M, AU - Crouch,Robert J, AU - Cerritelli,Susana M, Y1 - 2008/11/16/ PY - 2008/11/19/pubmed PY - 2009/2/4/medline PY - 2008/11/19/entrez SP - 96 EP - 110 JF - Nucleic acids research JO - Nucleic Acids Res. VL - 37 IS - 1 N2 - Eukaryotic RNase H2 is a heterotrimeric enzyme. Here, we show that the biochemical composition and stoichiometry of the human RNase H2 complex is consistent with the properties previously deduced from genetic studies. The catalytic subunit of eukaryotic RNase H2, RNASEH2A, is well conserved and similar to the monomeric prokaryotic RNase HII. In contrast, the RNASEH2B and RNASEH2C subunits from human and Saccharomyces cerevisiae share very little homology, although they both form soluble B/C complexes that may serve as a nucleation site for the addition of RNASEH2A to form an active RNase H2, or for interactions with other proteins to support different functions. The RNASEH2B subunit has a PIP-box and confers PCNA binding to human RNase H2. Unlike Escherichia coli RNase HII, eukaryotic RNase H2 acts processively and hydrolyzes a variety of RNA/DNA hybrids with similar efficiencies, suggesting multiple cellular substrates. Moreover, of five analyzed mutations in human RNASEH2B and RNASEH2C linked to Aicardi-Goutières Syndrome (AGS), only one, R69W in the RNASEH2C protein, exhibits a significant reduction in specific activity, revealing a role for the C subunit in enzymatic activity. Near-normal activity of four AGS-related mutant enzymes was unexpected in light of their predicted impairment causing the AGS phenotype. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/19015152/Contributions_of_the_two_accessory_subunits_RNASEH2B_and_RNASEH2C_to_the_activity_and_properties_of_the_human_RNase_H2_complex_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkn913 DB - PRIME DP - Unbound Medicine ER -