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

J 2014

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, Muriel JOURDAN et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{1217988,
   author = {Zálešák, Jan and Lourdin, Morgane and Krejčí, Lumír and Constant, JeanandFrancois and Jourdan, Muriel},
   article_location = {London},
   article_number = {7},
   doi = {http://dx.doi.org/10.1016/j.jmb.2013.12.022},
   keywords = {DNA lesion; NMR; abasic site; 8-oxoguanine; Fpg},
   language = {eng},
   issn = {0022-2836},
   journal = {Journal of Molecular Biology},
   title = {Structure and Dynamics of DNA Duplexes Containing a Cluster of Mutagenic 8-Oxoguanine and Abasic Site Lesions},
   url = {http://dx.doi.org/10.1016/j.jmb.2013.12.022},
   volume = {426},
   year = {2014}
}

TY  - JOUR
ID  - 1217988
AU  - Zálešák, Jan - Lourdin, Morgane - Krejčí, Lumír - Constant, Jean-Francois - Jourdan, Muriel
PY  - 2014
TI  - Structure and Dynamics of DNA Duplexes Containing a Cluster of Mutagenic 8-Oxoguanine and Abasic Site Lesions
JF  - Journal of Molecular Biology
VL  - 426
IS  - 7
SP  - 1524-1538
EP  - 1524-1538
PB  - Academic Press
SN  - 00222836
KW  - DNA lesion
KW  - NMR
KW  - abasic site
KW  - 8-oxoguanine
KW  - Fpg
UR  - http://dx.doi.org/10.1016/j.jmb.2013.12.022
L2  - http://dx.doi.org/10.1016/j.jmb.2013.12.022
N2  - 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.
ER  -

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. \textit{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.

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