Base flipping free energy profiles for damaged and undamaged DNA

Han Zheng, Yuqin Cai, Shuang Ding, Yijin Tang, Konstantin Kropachev, Yanzi Zhou, Lihua Wang, Shenglong Wang, Nicholas E. Geacintov, Yingkai Zhang, Suse Broyde

Research output: Contribution to journalArticlepeer-review


Lesion-induced thermodynamic destabilization is believed to facilitate β-hairpin intrusion by the human XPC/hHR23B nucleotide excision repair (NER) recognition factor, accompanied by partner-base flipping, as suggested by the crystal structure of the yeast orthologue (Min, J. H. and Pavletich, N. P. (2007) Nature 449, 570 -575). To investigate this proposed mechanism, we employed the umbrella sampling method to compute partner base flipping free energies for the repair susceptible 14R (+)-trans-anti-DB[a,l]P-N 2-dG modified duplex 11-mer, derived from the fjord region polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene, and for the undamaged duplex. Our flipping free energy profiles show that the adduct has a lower flipping barrier by ∼7.7 kcal/mol, consistent with its thermally destabilizing impact on the damaged DNA duplex and its susceptibility to NER.

Original languageEnglish (US)
Pages (from-to)1868-1870
Number of pages3
JournalChemical research in toxicology
Issue number12
StatePublished - Dec 20 2010

ASJC Scopus subject areas

  • Toxicology


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