Abstract
Significance Deamination of cytosine and adenine bases in DNA is one of the most common sources of genetic mutation in biology and a major driver of virus and tumor evolution. Recent studies have identified a novel class of DNA-repair enzyme from archaea and bacteria, designated endonuclease Q (EndoQ), which has unique activity to initiate the repair of both these deaminated lesions. Our X-ray crystallographic and biochemical analyses presented here reveal how EndoQ achieves high selectivity toward these chemically divergent substrates without cleaving undamaged DNA. We also demonstrate that EndoQ, as the only known nuclease that cleaves DNA at deoxyuridine nucleotide, is useful for studying DNA deamination and repair in mammalian systems.
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