DNA is a fragile organic molecule of finite chemical stability, capable of interacting with a variety of chemicals. In the context of the living cell this DNA reactivity is manifested as mutability. In addition to the chemical mutability, the perpetuation of DNA via imperfect replication is another source of DNA changeability. It is worth mentioning that DNA repair is error-tolerant and always leaves behind some lesions exist. Were repair mechanisms perfect, then the door of evolution would be locked. Risky rather than benign at individual level, mutations are the living things' long term strategy for survival and evolution. The creative power of mutations can explain why organisms have evolved special mechanisms to enhance mutagenesis under certain conditions. Hypermutation in bacteria under stress (SOS response) as well as hypermutation of immunoglobulin genes in response to antigen challenge in vertebrates are key examples. The present study is focused on spontaneous mutagenesis in Escherichia coli K-12. Spontaneous mutations are the net result of DNA damage and repair under normal physiological conditions. Bacterial DNA is loosely packed with proteins and occupies almost the entire cellular space. Therefore, it is extremely vulnerable to chemical attack, especially during replication and transcription, when the two DNA strands are separated. In the same arena, the cytoplasm, and at the same time, play also many small but highly reactive compounds. Although the collision of the latter with DNA seems to be unavoidable, to date the impact of ordinary cellular metabolites on spontaneous mutagenesis has not been systematically studied. In year 2012 we shall celebrate the 100 anniversary of the discovery of the carbonylamine reaction by the French chemist Louis Camille Maillard (Maillard, 1912). Here, we provide evidence that the Maillard reaction, referred to as non-enzymatic glycosylation or glycation in the literature, is an important endogenous source of spontaneous mutations in E. coli. Experimental data allowed us to estimate that glycation affects on average one per 105 to 104 nucleotides in the E. coli chromosome. Based on experimental evidence, we postulate the existence in E. coli of a novel DNA repair enzyme, DNA amadoriase or DNA deglycase, especially designed to combat glycation induced spontaneous mutagenesis in E. coli.

Department of Biology

Mironova, R. (Roumyana), Handzhiyski, Y. (Yordan), Niwa, T. (Toshimitsu), Berzal-Herranz, A. (Alfredo), Datsenko, K.A. (Kirill A.), Wanner, B.L. (Barry L.), … Golshani, A. (2010). Maillard reaction and spontaneous mutagenesis in Escherichia coli. In Bacterial DNA, DNA Polymerase and DNA Helicases (pp. 51–89).