Structure and Dynamics of DNA Duplexes Containing a Cluster of Mutagenic 8-Oxoguanine and Abasic Site Lesions

ZÁLEŠÁK, Jan, Morgane LOURDIN, Lumír KREJČÍ, Jean-Francois CONSTANT and Muriel JOURDAN. Structure and Dynamics of DNA Duplexes Containing a Cluster of Mutagenic 8-Oxoguanine and Abasic Site Lesions. Journal of Molecular Biology. London: Academic Press, 2014, vol. 426, No 7, p. 1524-1538. ISSN 0022-2836. Available from: https://dx.doi.org/10.1016/j.jmb.2013.12.022.

Basic information

• Original name: Structure and Dynamics of DNA Duplexes Containing a Cluster of Mutagenic 8-Oxoguanine and Abasic Site Lesions
• Authors: ZÁLEŠÁK, Jan (203 Czech Republic), Morgane LOURDIN (250 France), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution), Jean-Francois CONSTANT (250 France) and Muriel JOURDAN (250 France).
• Edition: Journal of Molecular Biology, London, Academic Press, 2014, 0022-2836.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 4.333
• RIV identification code: RIV/00216224:14110/14:00078633
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1016/j.jmb.2013.12.022
• UT WoS: 000334478000015
• Keywords in English: DNA lesion; NMR; abasic site; 8-oxoguanine; Fpg
• Tags: EL OK
• Tags: International impact, Reviewed

Abstract

Clustered DNA damage sites are caused by ionizing radiation. They are much more difficult to repair than are isolated single lesions, and their biological outcomes in terms of mutagenesis and repair inhibition are strongly dependent on the type, relative position and orientation of the lesions present in the cluster. To determine whether these effects on repair mechanism could be due to local structural properties within DNA, we used H-1 NMR spectroscopy and restrained molecular dynamics simulation to elucidate the structures of three DNA duplexes containing bistranded clusters of lesions. Each DNA sequence contained an abasic site in the middle of one strand and differed by the relative position of the 8-oxoguanine, staggered on either the 3' or the 5' side of the complementary strand. Their repair by base excision repair protein Fpg was either complete or inhibited. All the studied damaged DNA duplexes adopt an overall B-form conformation and the damaged residues remain intrahelical. No striking deformations of the DNA chain have been observed as a result of close proximity of the lesions. These results rule out the possibility that differential recognition of clustered DNA lesions by the Fpg protein could be due to changes in the DNA's structural features induced by those lesions and provide new insight into the Fpg recognition process.