Effect of cytosine methylation on DNA-DNA recognition at CpG steps.

Abstract:

:Although DNA methylation is a fundamental mechanism for repressing genetic activity, the influence of methyl groups on DNA conformation is found to be small. In this study, the role of cytosine methylation is analysed in the context of DNA condensation by examining its influence on DNA-DNA recognition processes. Previously CpG sites were found to act as sequence determinants for the close and specific self-fit of B-DNA helices into cross-overs. In the present study, the crystal structure of the B-DNA dodecamer d(ACCGCCGGCGCC) methylated at its central CpG sequence shows that the methyl groups do not interfere with DNA self-fitting. In contrast, the two methyl groups form a clamp, which traps the incoming phosphate in the groove-backbone interaction. This geometry allows the formation of two new C-H...O hydrogen bonds between the 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 methylation in genetic inactivation.

journal_name

J Mol Biol

authors

Mayer-Jung C,Moras D,Timsit Y

doi

10.1006/jmbi.1997.1137

subject

Has Abstract

pub_date

1997-07-18 00:00:00

pages

328-35

issue

3

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(97)91137-2

journal_volume

270

pub_type

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