Structure and recognition of sheared tandem G·A base pairs associated with human centromere DNA sequence at atomic resolution

Yi Gui Gao, Howard Robinson, Ruslan Sanishvili, Andrzej Joachimiak, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

G·A mismatched base pairs are frequently found in nucleic acids. Human centromere DNA sequences contain unusual repeating motifs, e.g., (GAATG)(n)·(CATTC)(n) found in the human chromosome. The purine-rich strand of this repeating pentamer sequence forms duplex and hairpin structures with unusual stability. The high stability of these structures is contributed by the 'sheared' G·A base pairs which present a novel recognition surface for ligands and proteins. We have solved the crystal structure, by the multiple- wavelength anomalous diffraction (MAD) method of d(CCGAATGAGG) in which the centromere core sequence motif GAATG is embedded. Three crystal forms were refined to near-atomic resolution. The structures reveal the detailed conformation of tandem G·A base pairs whose unique hydrogen-bonding surface has interesting interactions with bases, hydrated magnesium ions, cobalt(III)hexaammine, spermine, and water molecules. The results are relevant in understanding the structure associated with human centromere sequence in particular and G·A base pairs in nucleic acids (including RNA, like ribozyme) in general.

Original languageEnglish
Pages (from-to)16452-16460
Number of pages9
JournalBiochemistry
Volume38
Issue number50
DOIs
Publication statusPublished - Dec 14 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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