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Overview
Robert Crouch, who leads the Section on Formation of RNA, studies RNases H, enzymes that degrade RNA in RNA/DNA hybrids. Failure to degrade RNA in DNA can lead to loss of mitochondrial DNA, detrimental DNA recombination, and severe neurological defects. Type I RNase H is structurally and functionally related to an essential RNase H of the HIV-AIDS virus and could be a target for HIV drug therapy. In humans, defective Type II RNase H can result in Aicardi-Goutières syndrome (AGS), an encephalopathy that mimics in utero viral infection. A collaborative effort determined the structure of human RNase H2, a three-subunit protein, permitting localization in the 3-D structure of all presently known AGS mutations. Human RNase H2 can remove single ribonucleotides misincorporated in DNA as well as longer stretches of RNA/DNA hybrids, thereby helping to maintain genome stability.