Home WakeSpace Scholarship › Electronic Theses and Dissertations

Structural Studies of the Mammalian RNase H2 Heterotrimeric Complex

Electronic Theses and Dissertations

Item Files

Item Details

RNase H enzymes are endonucleases that specifically catalyze the hydrolysis of ribonucleotides in RNA:DNA hybrids. They are classified into type 1 or type 2 based on amino acid sequence similarity, structure, and biochemical properties. Type 1 RNase Hs require a minimum of four ribonucleotides whereas type 2 can recognize even a single ribonucleotide in a DNA duplex. Eukaryotic RNase H2 is a heterotrimeric complex of the H2A, H2B, and H2C proteins. Mutations in any of the genes encoding for the three proteins of the RNase H2 complex cause the rare autoimmune disease Aicardi Giouteres Syndrome. We determined the structure of the mammalian RNase H2 complex to better understand the molecular mechanisms behind RNase H2 mediated immune dysfunction. The structure has several unique features including the intimately associated nature of the H2B and H2C proteins that form a triple barrel motif. This motif is seen in several DNA binding proteins involved in transcription. Through DNA binding and mutational experiments, we show that the subcomplex formed by the H2B and H2C proteins has nucleic acid binding ability. The studies described in this thesis further our knowledge of RNase H2 enzymes, and shed light on fairly understudied pathways in RNA:DNA hybrid metabolism and autoimmunity.
autoimmune disease
enzyme complex
protein structure
RNase H2
Shaban, Nadine M. (author)
Hollis, Thomas (committee chair)
Alexander, Rebecca (committee member)
Lyles, Doug (committee member)
Hantgan, Roy (committee member)
Wang, Yuh-Hwa (committee member)
Perrino, Fred (committee member)
2012-01-18T09:35:22Z (accessioned)
2011 (issued)
Biochemistry and Molecular Biology (discipline)
10000-01-01 (liftdate)
forever (terms)
http://hdl.handle.net/10339/36415 (uri)
en (iso)
Wake Forest University
Structural Studies of the Mammalian RNase H2 Heterotrimeric Complex

Usage Statistics