Computational mapping reveals dramatic effect of Hoogsteen breathing on duplex DNA reactivity with formaldehyde.

ABSTRACT: Formaldehyde has long been recognized as a hazardous environmental agent highly reactive with DNA. Recently, it has been realized that due to the activity of histone demethylation enzymes within the cell nucleus, formaldehyde is produced endogenously, in direct vicinity of genomic DNA. Should it lead to extensive DNA damage? We address this question with the aid of a computational mapping method, analogous to X-ray and nuclear magnetic resonance techniques for observing weakly specific interactions of small organic compounds with a macromolecule in order to establish important functional sites. We concentrate on the leading reaction of formaldehyde with free bases: hydroxymethylation of cytosine amino groups. Our results show that in B-DNA, cytosine amino groups are totally inaccessible fo

SUBMITTER: Bohnuud T 

PROVIDER: S-EPMC3439909 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature