2L2V

NMR Solution Structures of -3 (3' staggered) Bistranded Abasic Site Lesions in DNA

Summary for 2L2V

• Entry DOI: 10.2210/pdb2l2v/pdb
• Related: 1yct 1ycw
• Descriptor: DNA_(5'-D(*CP*AP*GP*CP*TP*AP*TP*GP*(3DR)P*GP*AP*AP*GP*C)-3')_, DNA_(5'-D(*GP*CP*TP*TP*CP*AP*CP*AP*(3DR)P*AP*GP*CP*TP*G)-3')_ (2 entities in total)
• Functional Keywords: abasic lesion, bistranded dna lesions, clustered dna damage, multiple dna damage, ionizing radiation, dna
• Total number of polymer chains: 2
• Total formula weight: 8312.40

Authors

Hazel, R.D.,de los Santos, C. (deposition date: 2010-08-27, release date: 2011-07-13, Last modification date: 2024-05-01)

Primary citation

Hazel, R.D.,de los Santos, C.
NMR solution structures of clustered abasic site lesions in DNA: structural differences between 3'-staggered (-3) and 5'-staggered (+3) bistranded lesions.
Biochemistry, 49:8978-8987, 2010

PubMed Abstract: Ionizing radiation produces a distinctive pattern of bistranded clustered lesions in DNA. A relatively low number of clustered lesions may be lethal to cells when compared to a larger number of single lesions. Enzyme cleavage experiments suggest that the orientation of bistranded lesions causes differential recognition and removal of these lesions. Like that of a previous study of bistranded abasic site lesion [Hazel, R. D., Tian, K., and de los Santos, C. (2008) Biochemistry 47, 11909-11919], the aim of this investigation was to determine the structures of two DNA duplexes each containing two synthetic apurinic/apyrimidinic (AP) residues, positioned on opposite strands and separated by two base pairs. In the first duplex, the AP residues are staggered in the 3' orientation [-3 duplex, (AP)(2)-3 duplex], while in the second duplex, the AP residues are staggered in the 5' orientation [+3 duplex, (AP)(2)+3 duplex]. NOESY spectra recorded in 100 and 10% D(2)O buffer solutions allowed the assignment of the nonexchangeable and exchangeable protons, respectively, for each duplex. Cross-peak connectivity in the nonexchangeable proton spectra indicates that the duplex is a regular right-handed helix with the AP residues and orphan bases located inside the duplexes. The exchangeable proton spectra establish the formation of Watson-Crick G·C alignment for the two base pairs between the lesion sites in both duplexes. Distance-restrained molecular dynamics simulation confirmed the intrahelical orientations of the AP residues. The proximity of the AP residues across the minor groove of the -3 duplex and across the major groove in the +3 duplex is similar to their locations in the case of -1 and +1 clusters. This difference in structure may be a key factor in the differential recognition of bistranded AP lesions by human AP endonuclease.

PubMed: 20825249
DOI: 10.1021/bi101021e

Experimental method

SOLUTION NMR