Nucleic Acids Research, 2001, Vol. 29, No. 7 1458-1463
© 2001 Oxford University Press
Site-specifically located 8-amino-2'-deoxyguanosine: thermodynamic stability and mutagenic properties in Escherichia coli
Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060, USA and 1Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
2-Nitropropane (2-NP), an important industrial solvent and a component of cigarette smoke, is mutagenic in bacteria and carcinogenic in rats. 8-Amino-2'-deoxyguanosine (8-amino-dG) is one of the types of DNA damage found in liver, the target organ in 2-NP-treated rats. To investigate the thermodynamic properties of 8-amino-dG opposite each of the four DNA bases, we have synthesized an 11mer, d(CCATCG*CTACC), in which G* represents the modified base. By annealing a complementary DNA strand to this modified 11mer, four sets of duplexes were generated each containing one of the four DNA bases opposite the lesion. Circular dichroism studies indicated that 8-amino-dG did not alter the global helical properties of natural right-handed B-DNA. The thermal stability of each duplex was examined by UV melting measurements and compared with its unmodified counterpart. For the unmodified 11mer, the relative stability of the complementary DNA bases opposite G was in the order C > T > G > A, as determined from their –
G° values. The free energy change of each modified duplex was lower than its unmodified counterpart, except for the G*:G pair that exhibited a higher melting transition and a larger –G° than the G:G duplex. Nevertheless, the stability of the modified 11mer duplex also followed the order C > T > G > A when placed opposite 8-amino-dG. To explore if 8-amino-dG opposite another 8-amino-dG has any advantage in base pairing, a G*:G* duplex was evaluated, which showed that the stability of this duplex was similar to the G*:G duplex. Mutagenesis of 8-amino-dG in this sequence context was studied in Escherichia coli, which showed that the lesion is weakly mutagenic (mutation frequency 
10–3) but still can induce a variety of targeted and semi-targeted mutations.
* To whom correspondence should be addressed. Tel: +1 860 486 3965; Fax: +1 860 486 2981; Email: ashis.basu{at}uconn.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. R. Meneni, R. D'Mello, G. Norigian, G. Baker, L. Gao, M. P. Chiarelli, and B. P. Cho Sequence effects of aminofluorene-modified DNA duplexes: thermodynamic and circular dichroism properties Nucleic Acids Res., January 30, 2006; 34(2): 755 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Avino, M. Frieden, J. C. Morales, B. Garcia de la Torre, R. Guimil Garcia, F. Azorin, J. L. Gelpi, M. Orozco, C. Gonzalez, and R. Eritja Properties of triple helices formed by parallel-stranded hairpins containing 8-aminopurines Nucleic Acids Res., June 15, 2002; 30(12): 2609 - 2619. [Abstract] [Full Text] [PDF]
|
|