title: Whether 2-aminopurine induces incorporation errors at the DNA replication? A quantum-mechanical answer on the actual biological issue.
abstract: In this paper, we consider the mutagenic properties of the 2-aminopurine (2AP), which has intrigued molecular biologists, biophysicists and physical chemists for a long time and been widely studied by both experimentalists and theorists. We have shown for the first time using QM calculations, that 2AP very effectively produces incorporation errors binding with cytosine (C) into the wobble (w) C·2AP(w) mispair, which is supported by the N4H⋯N1 and N2H⋯N3 H-bonds and is tautomerized into the Watson-Crick (WC)-like base mispair C*·2AP(WC) (asterisk denotes the mutagenic tautomer of the base), that quite easily in the process of the thermal fluctuations acquires enzymatically competent conformation. 2AP less effectively produces transversions forming the wobble mispair with A base - A·2AP(w), stabilized by the participation of the N6H⋯N1 and N2H⋯N1 H-bonds, followed by further tautomerization A·2AP(w) → A*·2AP(WC) and subsequent conformational transition A*·2AP(WC) → A*·2APsynthus acquiring enzymatically competent structure. In this case, incorporation errors occur only in those case, when 2AP belongs to the incoming nucleotide. Thus, answering the question posed in the title of the article, we affirm for certain that 2AP induces incorporation errors at the DNA replication. Obtained results are consistent well with numerous experimental data.
authors: a Department of Molecular and Quantum Biophysics , Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine , 150 Akademika Zabolotnoho Str., Kyiv 03680 , Ukraine.|b Department of Molecular Biotechnology and Bioinformatics , Institute of High Technologies, Taras Shevchenko National University of Kyiv , 2-h Akademika Hlushkova Ave., Kyiv 03022 , Ukraine.
authors: Ol'ha O
authors: http://orcid.org/0000-0002-8929-293X
authors: OO
authors: Brovarets'
authors: c Computer Science Department, Bioinformatics and High Performance Computing (BIO-HPC) Research Group , Universidad Católica San Antonio de Murcia (UCAM) , Murcia 30107 , Spain.
authors: Horacio
authors: http://orcid.org/0000-0003-4468-7898
authors: H
authors: Pérez-Sánchez
mesh_terms: D015075:2-Aminopurine / Q000737:chemistry*; D020137:Base Pair Mismatch; D020029:Base Pairing; D004261:DNA Replication; D006860:Hydrogen Bonding; D008958:Models, Molecular; D017354:Point Mutation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D015075:2-Aminopurine
keywords: 2-aminopurine; DNA replication; Watson–Crick↔wobble tautomeric transition; incorporation errors; induced point mutations; mutagenicity