Bret Freudenthal @freudlab.bsky.social · 11/08/20263/ Why? Not because the lesion looks different. Our group solved Cryo-EM structures at SHL+2, +3, +4, and -6 all show 8oxoG in the syn conformation, Hoogsteen paired with A, matching non-nucleosomal DNA. 100
Bret Freudenthal @freudlab.bsky.social · 11/08/20264/ MD simulations from the Bignon lab agree: the same two-state conformational exchange and the same local backbone perturbations in nucleosomal and non-nucleosomal DNA. 100
Bret Freudenthal @freudlab.bsky.social · 11/08/20265/ MUTYH needs to engage both strands with its N- and C-terminal domains. Modeling shows it cannot do that in an NCP without clashing into the histones. Steric exclusion, not altered lesion presentation, is the barrier. 100
