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On the role of steric clashes in methylation control of restriction endonuclease activity

Mierzejewska, Karolina and Bochtler, Matthias and Czapinska, Honorata (2015) On the role of steric clashes in methylation control of restriction endonuclease activity. Nucleic acids research . ISSN 1362-4962


Official URL: http://nar.oxfordjournals.org/content/early/2015/1...


Restriction-modification systems digest non-methylated invading DNA, while protecting host DNA against the endonuclease activity by methylation. It is widely believed that the methylated DNA would not 'fit' into the binding site of the endonuclease in the productive orientation, and thus steric clashes should account for most of the protection. We test this concept statistically by grafting methyl groups in silico onto non-methylated DNA in co-crystal structures with restriction endonucleases. Clash scores are significantly higher for protective than non-protective methylation (P < 0.05% according to the Wilcoxon rank sum test). Structural data alone are sufficient to distinguish between protective and non-protective DNA methylation with 90% confidence and decision thresholds of 1.1 Å and 48 Å3 for the most severe distance-based and cumulative volume-based clash with the protein, respectively (0.1 Å was deducted from each interatomic distance to allow for coordinate errors). The most severe clashes are more pronounced for protective methyl groups attached to the nitrogen atoms (N6-methyladenines and N4-methylcytosines) than for C5-methyl groups on cytosines. Cumulative clashes are comparable for all three types of protective methylation.

Item Type:Article
Additional Information:This is an Open Access article
Subjects:Q Science > Q Science (General)
Divisions:Department of Bioinformatics
ID Code:1097
Deposited By: Prof. Matthias Bochtler
Deposited On:22 Dec 2015 13:01
Last Modified:11 Jan 2016 09:22

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