A Hoogsteen Base Pair Embedded in Undistorted B-DNA
Hoogsteen base pairs within duplex DNA typically
are only observed in regions containing significant
distortion or near sites of drug intercalation. We
report here the observation of a Hoogsteen base
pair embedded within undistorted, unmodified
B-DNA. The Hoogsteen base pair, consisting of a
syn adenine base paired with an anti thymine base,
is found in the 2.1 Å
resolution structure of the
MATa2 homeodomain bound to DNA in a region
where a specifically and a non-specifically bound
homeodomain contact overlapping sites. NMR
studies of the free DNA show no evidence of
Hoogsteen base pair formation, suggesting that
protein binding favors the transition from a
Watson-Crick to a Hoogsteen base pair. Molecular
dynamics simulations of the homeodomainąDNA
complex support a role for the non-specifically
bound protein in favoring Hoogsteen base pair
formation. The presence of a Hoogsteen base pair in
the crystal structure of a protein-DNA complex
raises the possibility that Hoogsteen base pairs
could occur within duplex DNA and play a hitherto
unrecognized role in transcription, replication and
other cellular processes.
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