Mechanisms of Mutagenic DNA Nucleobase Damages and Their Chemical and Enzymatic Repairs Investigated by Quantum Chemical Methods

摘要: A cells genetic information, its 'blueprint of life', is contained within DNA. This biologically important molecule, however, can be attacked by high–energy ionizing radiation and oxidizing agents resulting in a range possible damage. For instance, nucleobases undergo chemical modifications or degradation such as oxidation, deamination, alkylation cleaved from the sugar-phosphate backbone. (De Bont & van Larebeke 2004; Friedberg et al. Hecht 1999; Kamiya 1998; Labet 2008a; Lindahl 1993; Lysetska 2002; Neeley Essigmann 2006; Rydberg 1982; Taylor 1994; Wang 2008) Similarly, deoxyribose sugar moieties may also various modifications. These events lead further to formation DNA– DNA DNA–protein cross–links DNA–strand breaks. (Kumar Sevilla 2010; Lipfert 2004) Importantly, damage significantly affect replication transcription. ultimately result cell apoptosis protein mutations pathological diseases cancer. (Pages Fuchs 2002) Experimentally, there have been numerous detailed vivo vitro investigations into processes pathways involved (See, for Kumar Mishina 2006, Wetmore 2001) Radiolysis experiments with photometric, electrochemical electron paramagnetic resonance detection, enzymatic inhibition mutagenesis studies identified large number reaction intermediates rate constants many repair processes. more in-depth reviews experimental on reader directed relevant chapters this present book. Unfortunately, uncertainties questions still remain about repair. Computational chemistry provides an alternate complementary approach obtaining deeper understanding part because it not only applied systems that are amenable investigation but those