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)
- Pacific Northwest Lab., Richland, WA (United States)
The molecular link between sunlight exposure and skin cancer can be traced to the formation of cyclobutane pyrimidine dimers together with (6-4) photoadducts of pyrimidines in DNA upon exposure to UV radiation. The mutagenicity of these lesions is frequently explained by miscoding during DNA replication due to perturbations of base-pairing interactions. However the mutagenicity of UV photoproducts depends of their sequence context, suggesting that more global structural changes in DNA contribute to mutation induction. One of the most effective protections against the deleterious effects of cyclobutane pyrimidine dimers is the wide range of repair of this lesion by different enzymatic pathways. This paper presents the results of a 200 ps molecular dynamics simulation on the dodecarner 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.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mount Sinai School of Medicine, New York, NY (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- AC06-76RL01830; FG02-88ER60675
- OSTI ID:
- 134996
- Report Number(s):
- PNL-SA-26165; CONF-9510243-1; ON: DE96002714; TRN: 95:008645
- Resource Relation:
- Conference: International workshop on radiation damage in DNA: relationships at early times, Gleneden, OR (United States), 1-6 Oct 1995; Other Information: PBD: Oct 1995
- Country of Publication:
- United States
- Language:
- English
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