Enthalpy-entropy Contribution to Carcinogen-induced DNA Conformational Heterogeneity

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2009 Dec 8

PMID 19961237

Citations 6

Authors

Fengting Liang

Bongsup P Cho

Affiliations

Soon will be listed here.

Abstract

DNA damage by adduct formation is a critical step for the initiation of carcinogenesis. Aromatic amines are strong inducers of environmental carcinogenesis. Their DNA adducts are known to exist in an equilibrium between the major groove (B) and base-displaced stacked (S) conformations. However, the factors governing such heterogeneity remain unclear. Here we conducted extensive calorimetry/NMR/CD studies on the model DNA lesions caused by fluorinated 2-aminfluorene (FAF) and 4-aminobiphenyl (FABP) in order to gain thermodynamic and kinetic insights into the S/B conformational equilibrium. We demonstrate that there are large differences in enthalpy-entropy compensations for FABP and FAF. The small and flexible FABP exclusively adopts the less perturbed B conformer with small enthalpy (DeltaDeltaH-2.7 kcal/mol)/entropy (DeltaDeltaS-0.7 eu) change. In contrast, FAF stacks better and exists as a mixture of B and S conformers with large enthalpy (DeltaDeltaH-13.4 kcal/mol)/entropy (DeltaDeltaS-34.2 eu) compensation. van't Hoff analysis of dynamic (19)F NMR data indicated DeltaH(B<-->S) = 4.1 kcal/mol in favor of the B conformer and DeltaS(B<-->S) = 15.6 cal mol(-1) K(-1) in favor of the intercalated S conformer. These findings demonstrate that the favorable entropy of the S conformer over B conformer determines the S/B population ratios at physiological temperatures.

Citing Articles

DNA base sequence effects on bulky lesion-induced conformational heterogeneity during DNA replication.

Cai A, Wilson K, Patnaik S, Wetmore S, Cho B Nucleic Acids Res. 2018; 46(12):6356-6370.

PMID: 29800374 PMC: 6158707. DOI: 10.1093/nar/gky409.

Repair-Resistant DNA Lesions.

Geacintov N, Broyde S Chem Res Toxicol. 2017; 30(8):1517-1548.

PMID: 28750166 PMC: 5569670. DOI: 10.1021/acs.chemrestox.7b00128.

Conformational insights into the lesion and sequence effects for arylamine-induced translesion DNA synthesis: 19F NMR, surface plasmon resonance, and primer kinetic studies.

Jain V, Vaidyanathan V, Patnaik S, Gopal S, Cho B Biochemistry. 2014; 53(24):4059-71.

PMID: 24915610 PMC: 4075988. DOI: 10.1021/bi5003212.

Structure and thermodynamic insights on acetylaminofluorene-modified deletion DNA duplexes as models for frameshift mutagenesis.

Sandineni A, Lin B, MacKerell Jr A, Cho B Chem Res Toxicol. 2013; 26(6):937-51.

PMID: 23688347 PMC: 3733349. DOI: 10.1021/tx400116n.

Unusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factor.

Jain V, Hilton B, Lin B, Patnaik S, Liang F, Darian E Nucleic Acids Res. 2012; 41(2):869-80.

PMID: 23180767 PMC: 3553991. DOI: 10.1093/nar/gks1077.

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