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.

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.