Dynamics in psoralen-damaged DNA by 1H-detected natural abundance 13C NMR spectroscopy

Biochemistry
H Peter Spielmann

Abstract

The dynamics of the DNA oligomer d(GCGTACGC)2 and the 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen-DNA furanside monoadduct (MAf) of this oligomer have been determined from NMR relaxation parameters. Longitudinal and transverse 13C relaxation rates and heteronuclear NOE relaxation data have been measured at natural abundance and have been analyzed in the context of the Lipari and Szabo model-free formalism. The generalized order parameters for methine carbons in the octamer sequence d(GCGTACGC)2 (UM) are relatively and uniformly high for the entire molecule. The generalized order parameters for methine carbons in the MAf are significantly lower for the deoxyribose bearing the damaged thymidine base and for the bases flanking the lesion on the undamaged strand, indicating additional conformational flexibility due to the lesion. The order parameters for the bases on the damaged strand flanking the lesion remain high. Analysis of the relaxation data indicates substantial chemical exchange for the adenosine residues in the UM TpA site, and this chemical exchange is quenched upon MAf formation. These data are discussed in terms of a model for DNA damage recognition by the nucleotide excision repair system.

References

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Citations

Oct 8, 2005·Journal of Biomolecular NMR·Elke Duchardt, Harald Schwalbe
Jan 18, 2011·Nature Structural & Molecular Biology·Marcin JaciukMarcin Nowotny
Jan 5, 2001·Nucleic Acids Research·P KhandelwalR V Hosur
Feb 23, 2010·Trends in Biochemical Sciences·David M Wilson, Michael M Seidman
Aug 27, 2014·The Journal of Physical Chemistry. B·Maryna TaranovaIoan Andricioaei
Dec 22, 2016·International Journal of Molecular Sciences·Qiulong ZhangGe Zhang

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