A Hoogsteen base pair embedded in undistorted B-DNA

Jun Aishima, Rossitza K. Gitti, Joyce E. Noah, Hin Hark Gan, Tamar Schlick, Cynthia Wolberger

Research output: Contribution to journalReview articlepeer-review

Abstract

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 MATα2 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 homeodomain-DNA 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.

Original languageEnglish (US)
Pages (from-to)5244-5252
Number of pages9
JournalNucleic acids research
Volume30
Issue number23
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Genetics

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