期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 87, 期 1, 页码 25-30出版社
SPRINGER
DOI: 10.1007/s00109-008-0422-3
关键词
Aicardi-Goutieres syndrome; RNaseH2; Nuclease; Immune activation
资金
- National Institutes of Health [GM069962]
- Alliance for Lupus Research [67692]
- American Cancer Society [RSG-04-187-01-GMC]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM069962] Funding Source: NIH RePORTER
Mutations in the genes encoding the RNaseH2 and TREX1 nucleases have been identified in patients with Aicardi-Goutieres syndrome (AGS). To determine if the AGS RNaseH2 mutations result in the loss of nuclease activity, the human wild-type RNaseH2 and four mutant complexes that constitute the majority of mutations identified in AGS patients have been prepared and tested for ribonuclease H activity. The heterotrimeric structures of the mutant RNaseH2 complexes are intact. Furthermore, the ribonuclease H activities of the mutant complexes are indistinguishable from the wild-type enzyme with the exception of the RNaseH2 subunit A (Gly37Ser) mutant, which exhibits some evidence of altered nuclease specificity. These data indicate that the mechanism of RNaseH2 dysfunction in AGS cannot be simply explained by loss of ribonuclease H activity and points to a more complex mechanism perhaps mediated through altered interactions with as yet identified nucleic acids or protein partners.
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