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.Základní údaje
Originální název
Structure and Dynamics of DNA Duplexes Containing a Cluster of Mutagenic 8-Oxoguanine and Abasic Site Lesions
Autoři
ZÁLEŠÁK, Jan (203 Česká republika), Morgane LOURDIN (250 Francie), Lumír KREJČÍ (203 Česká republika, garant, domácí), Jean-Francois CONSTANT (250 Francie) a Muriel JOURDAN (250 Francie)
Vydání
Journal of Molecular Biology, London, Academic Press, 2014, 0022-2836
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10600 1.6 Biological sciences
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 4.333
Kód RIV
RIV/00216224:14110/14:00078633
Organizační jednotka
Lékařská fakulta
UT WoS
000334478000015
Klíčová slova anglicky
DNA lesion; NMR; abasic site; 8-oxoguanine; Fpg
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 21. 4. 2020 14:42, Mgr. Marie Šípková, DiS.
Anotace
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.