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• W1966454328 startingPage "91" @default.
• W1966454328 abstract "E. coli MutY excises adenine from duplex DNA when it is mispaired with the mutagenic oxidative lesion 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG). While E. coli MutY has been extensively studied, a detailed kinetic analysis of a mammalian MutY homologue has been inhibited by poor overexpression in bacterial hosts. This current work is the first detailed study of substrate recognition and repair of mismatched DNA by a mammalian adenine glycosylase, the murine MutY homologue (mMYH). Similar to E. coli MutY, the processing of OG:A substrates by mMYH is biphasic, indicating that product release is rate-limiting. Surprisingly, the intrinsic rates of adenine removal from both OG:A and G:A substrates by mMYH are diminished ( approximately 10-fold) compared to E. coli MutY. However, similar to E. coli MutY, the rate of adenine removal is approximately nine-fold faster with an OG:A- than a G:A-containing substrate. Interestingly, the rate of removal of 2-hydroxyadenine mispaired with OG or G in duplex DNA by mMYH was similar to the rate of adenine removal from the analogous context. In contrast, 2-hydroxyadenine removal by E. coli MutY was significantly reduced compared to adenine removal opposite both OG and G. Furthermore, dissociation constant measurements with duplexes containing noncleavable 2'-deoxyadenosine analogues indicate that mMYH is less sensitive to the structure of the base mispaired with OG or G than MutY. Though in many respects the catalytic behavior of mMYH is similar to E. coli MutY, the subtle differences may translate into differences in their in vivo functions." @default.
• W1966454328 created "2016-06-24" @default.
• W1966454328 creator A5025066738 @default.
• W1966454328 creator A5050502321 @default.
• W1966454328 date "2005-01-01" @default.
• W1966454328 modified "2023-09-25" @default.
• W1966454328 title "DNA damage recognition and repair by the murine MutY homologue" @default.
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• W1966454328 doi "https://doi.org/10.1016/j.dnarep.2004.08.004" @default.
• W1966454328 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15533841" @default.
• W1966454328 hasPublicationYear "2005" @default.
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