TY - JOUR
T1 - Base flipping free energy profiles for damaged and undamaged DNA
AU - Zheng, Han
AU - Cai, Yuqin
AU - Ding, Shuang
AU - Tang, Yijin
AU - Kropachev, Konstantin
AU - Zhou, Yanzi
AU - Wang, Lihua
AU - Wang, Shenglong
AU - Geacintov, Nicholas E.
AU - Zhang, Yingkai
AU - Broyde, Suse
PY - 2010/12/20
Y1 - 2010/12/20
N2 - 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.
AB - 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.
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U2 - 10.1021/tx1003613
DO - 10.1021/tx1003613
M3 - Article
C2 - 21090780
AN - SCOPUS:78650497367
SN - 0893-228X
VL - 23
SP - 1868
EP - 1870
JO - Chemical research in toxicology
JF - Chemical research in toxicology
IS - 12
ER -