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

G . A mismatched base pairs are frequently found in nucleic acids. Human ce ntromere DNA sequences contain unusual repeating motifs, e.g., (GAATG)(n).( CATTC)(n), found in the human chromosome. The purine-rich strand of this re peating pentamer sequence forms duplex and hairpin structures with unusual stability. The high stability of these structures is contributed by the "sh eared" G A base pairs which present a novel recognition surface for ligands and proteins. We have solved the crystal structure, by the multiple-wavele ngth anomalous diffraction (MAD) method of d(CCGAATGAGG) in which the centr omere core sequence motif GAATG is embedded. Three crystal forms were refin ed to near-atomic resolution. The structures reveal the detailed conformati on of tandem G A base pairs whose unique hydrogen-bonding surface has inter esting interactions with bases, hydrated magnesium ions, cobalt(III)hexaamm ine, spermine, and water molecules. The results are relevant in understandi ng the structure associated with human centromere sequence in particular an d G . A base pairs in nucleic acids (including RNA, like ribozyme) in gener al.