Crystallographic studies on damaged DNAsIV. N~4-methoxycytosine shows a second face for Watson-Crick Base-pairing, Leading to purine transition mutagenesis

摘要

To investigate the mutation mechanism of purine transitions in DNA damaged with methoxyamine, a DNA dodecamer with the sequence d(CGCAAATTmo~4CGCG), where mo~4C is 2'-deoxy-N~4-methoxycytidine, has been synthesized and the crystal structure determined by X-ray analysis. The duplex structure is similar to that of the original undamaged B-form dodecamer, indicating that the methoxylation does not affect the overall DNA conformation. Electron density maps clearly show that the two mo~4C residues form Watson-Crick-type base pairs with the adenine residues of the opposite strand and that the methoxy groups of mo~4C adopt the anti conformation to N~3 around the C~4-N~4 bond. For the pair formation through hydrogen bonds the mo~4C residues are in the imino tautomeric state. Together with previous work, the present work establishes that the methoxylated cytosine residue can present two alternate faces for Watson-Crick base-pairing, thanks to the amino<->imino tautomerism allowed by methoxylation. Based on this property, two gene transition routes are proposed.