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

ABSTRACT: 2-Acetylaminofluorene (AAF) is a prototype arylamine carcinogen that forms C8-substituted dG-AAF and dG-AF as the major DNA lesions. The bulky N-acetylated dG-AAF lesion can induce various frameshift mutations depending on the base sequence around the lesion. We hypothesized that the thermodynamic stability of bulged-out slipped mutagenic intermediates (SMIs) is directly related to deletion mutations. The objective of the present study was to probe the structural/conformational basis of various dG-AAF-induced SMIs formed during translesion synthesis. We performed spectroscopic, thermodynamic, and molecular dynamics studies of several AAF-modified 16-mer model DNA duplexes, including fully paired and -1, -2, and -3 deletion duplexes of the 5'-CTCTCGATG[FAAF]CCATCAC-3' sequence and an additi

SUBMITTER: Sandineni A 

PROVIDER: S-EPMC3733349 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature