Conformational and Thermodynamic Properties Modulate the Nulceotide Excision Repair of 2-Aminofluorene and 2-Acetylaminofluorene dG Adducts in the NarI Sequence

Authors

Vipin Jain
Benjamin Hilton
Satyakam Patnaik
Yue Zou
M. Paul Chiarelli, Loyola University ChicagoFollow
Bongsup P. Cho

Document Type

Article

Publication Date

1-2012

Publication Title

Nucleic Acids Research

Volume

40

Issue

9

Pages

3939–3951

Publisher Name

Oxford University Press

Abstract

Nucleotide excision repair (NER) is a major repair pathway that recognizes and corrects various lesions in cellular DNA. We hypothesize that damage recognition is an initial step in NER that senses conformational anomalies in the DNA caused by lesions. We prepared three DNA duplexes containing the carcinogen adduct N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-acetylaminofluorene (FAAF) at G(1), G(2) or G(3) of NarI sequence (5'-CCG(1)G(2)CG(3)CC-3'). Our (19)F-NMR/ICD results showed that FAAF at G(1) and G(3) prefer syn S- and W-conformers, whereas anti B-conformer was predominant for G(2). We found that the repair of FAAF occurs in a conformation-specific manner, i.e. the highly S/W-conformeric G(3) and -G(1) duplexes incised more efficiently than the B-type G(2) duplex (G(3)∼G(1)> G(2)). The melting and thermodynamic data indicate that the S- and W-conformers produce greater DNA distortion and thermodynamic destabilization. The N-deacetylated N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluorene (FAF) adducts in the same NarI sequence are repaired 2- to 3-fold less than FAAF: however, the incision efficiency was in order of G(2)∼G(1)> G(3), a reverse trend of the FAAF case. We have envisioned the so-called N-acetyl factor as it could raise conformational barriers of FAAF versus FAF. The present results provide valuable conformational insight into the sequence-dependent UvrABC incisions of the bulky aminofluorene DNA adducts.

Comments

Author Posting. © Jain et al., 2012. This article is posted here by permission of the authors for personal use, not for redistribution. The article was published in Nucleic Acids Research, Volume 40, Issue 9, January 2012, http://dx.doi.org/10.1093/nar/gkr1307

Recommended Citation

Jain, V, B Hilton, S Patnaik, Y Zou, MP Chiarelli, and BP Cho. "Conformational and Thermodynamic Properties Modulate the Nulceotide Excision Repair of 2-Aminofluorene and 2-Acetylaminofluorene dG Adducts in the NarI Sequence." Nucleic Acids Research 40(9), 2012.

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Copyright Statement

© Jain et al., 2012.