Distribution of ions around thymine dimer containing DNA: A possible recognition element for endonuclease V
- Mount Sinai School of Medicine, New York, NY (United States). Dept. of Physiology and Biophysics
- Pacific Northwest Lab., Richland, WA (United States)
In spite of the high resolution X-ray crystal structure of endonuclease V and numerous site directed mutagenesis studies, the mechanism by which it recognizes the pyrimidine dimer lesion in DNA is still obscure. NMR studies performed on DNA oligonucleotides containing cis,syn-pyrimidine dimers showed that the distortions caused by the lesion are surprisingly small. Nevertheless, endonuclease V is able to recognize this change with very high fidelity. Since distortions of DNA structure are usually associated with changes in the electrostatic shielding by counterions and in solvation of DNA it is possible that the enzyme is acutely sensitive to this property, as is demonstrated by the dependence of the scanning ability on ionic strength. This paper presents the results of a 200 ps molecular dynamics simulation on the dodecamer d(CGCGAATTCGCG){sub 2} containing a cis,syn-cyclobutane thymine dimer, explicit water and counterions. The averaged structure calculated from the simulation shows good agreement with the available NMR data. The distribution of counterions around the damaged DNA is different from that around a non-damaged DNA and suggests a possible mechanism of damage recognition by the enzyme.
- DOE Contract Number:
- FG02-88ER60675; AC06-76RL01830
- OSTI ID:
- 400744
- Report Number(s):
- CONF-9410280--; ISBN 0-935470-90-5
- Country of Publication:
- United States
- Language:
- English
Similar Records
Computational simulations of DNA distortions by a cis,syn-cyclobutane thymine dimer lesion
Solution-state Structure of a DNA Dodecamer Duplex Containing a Cis-syn Thymine Cyclobutane Dimer, the Major UV Photoproduct of DNA.