Effect of 8-oxoguanine on DNA structure and deformability

Tomáš Dršata, Mahmut Kara, Martin Zacharias, Filip Lankaš

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


8-Oxoguanine (oxoG) is an abundant product of oxidative DNA damage. It is removed by repair glycosylases, but exactly how the enzymes recognize oxoG in the large surplus of undamaged bases is not fully understood. The lesion may induce changes in the properties of naked DNA that facilitate the recognition. In this work, we assess the effect of oxoG on DNA structure and mechanical deformability. We performed extensive unrestrained, atomic resolution molecular dynamics simulations to parametrize a nonlocal, rigid base mechanical model of DNA. Our data indicate that oxoG induces unwinding of the base pair step at the 5′-side of the lesion. This brings the damaged DNA closer to its conformation in the initial complex with bacterial glycosylase MutM. The untwisting is partially caused by different BII substate populations and is further enhanced by the base-sugar repulsion within oxoG. On the other hand, our analysis shows that damaged and undamaged DNA have very similar harmonic stiffness. These results suggest an indirect readout component of the MutM-DNA initial complex formation. They also help one to understand the effect of oxoG on the formation of nucleosomes and looped gene regulatory complexes.

Original languageEnglish
Pages (from-to)11617-11622
Number of pages6
JournalJournal of Physical Chemistry B
Issue number39
StatePublished - 3 Oct 2013
Externally publishedYes


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