EFFECT OF CYTOSINE METHYLATION ON DNA-DNA RECOGNITION AT CPG STEPS

Although DNA methylation is a fundamental mechanism for repressing gen etic activity, the influence of methyl groups on DNA conformation is f ound to be small. In this study, the role of cytosine methylation is a nalysed in the context of DNA condensation by examining its influence on DNA-DNA recognition processes. Previously CpG sites were found to a ct as sequence determinants for the close and specific self-fit of B-D NA helices into cross-overs. In the present study, the crystal structu re of the B-DNA dodecamer d(ACCGCCGGCGCC) methylated at its central Cp G sequence shows that the methyl groups do nest interfere with DNA sel f-fitting. In contrast the two methyl groups form a clamp, which traps the incoming phosphate in the groove-backbone interaction. This geome try allows the formation of two new C-H ... O hydrogen bonds between t he methyl groups and. the anionic oxygen atoms of the phosphate, which may further stabilize the interaction. This finding relates cytosine methylation to the formation of higher-order DNA structures and could provide new insights for understanding the mode of action of DNA methy lation in genetic inactivation. (C) 1997 Academic Press Limited.