DNA containing a cluster of 8-oxo-guanine and abasic site lesion: alpha anomer
Structure:
DNA (5'-d( Cp Gp Cp Tp Cp (Orp)p Cp Ap Cp Gp C)-3'). Chain: a. Engineered: yes. DNA (5'-d( Gp Cp Gp Tp Gp Gp Gp Ap (8Og)p Cp G)-3'). Chain: b. Engineered: yes
Source:
Synthetic: yes. Synthetic: yes
NMR struc:
10 models
Authors:
J.Zalesak,M.Jourdan,M.Lourdin,J.Constant
Key ref:
J.Zálešák
et al.
(2014).
Structure and dynamics of DNA duplexes containing a cluster of mutagenic 8-oxoguanine and abasic site lesions.
J Mol Biol,
426,
1524-1538.
PubMed id: 24384094
DOI: 10.1016/j.jmb.2013.12.022
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 (1)H 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.
Links
