Escherichia coli DNA glycosylase Mug: a growth-regulated enzyme required for mutation avoidance in stationary-phase cells.
The Escherichia coli DNA glycosylase Mug excises 3,N(4)-ethenocytosines (epsilon C) and uracils from DNA, but its biological function is obscure. This is because epsilon C is not found in E. coli DNA, and uracil-DNA glycosylase (Ung), a distinct enzyme, is much more efficient at removing uracils from DNA than Mug. We find that Mug is overexpressed as cells enter stationary phase, and it is maintained at a fairly high level in resting cells. This is true of cells grown in rich or minimal media, and the principal regulation of mug is at the level of mRNA. Although the expression of mug is strongly dependent on the stationary-phase sigma factor, sigma(S), when cells are grown in minimal media, it shows only a modest dependence on sigma(S) when cells are grown in rich media. When mug cells are maintained in stationary phase for several days, they acquire many more mutations than their mug(+) counterparts. This is true in ung as well as ung(+) cells, and a majority of new mutations may not be C to T. Our results show that the biological role of Mug parallels its expression in cells. It is expressed poorly in exponentially growing cells and has no apparent role in mutation avoidance in these cells. In contrast, Mug is fairly abundant in stationary-phase cells and has an important anti-mutator role at this stage of cell growth. Thus, Mug joins a very small coterie of DNA repair enzymes whose principal function is to avoid mutations in stationary-phase cells.
Mokkapati
S K
SK
Department of Chemistry, 463 Chemistry Building, Wayne State University, Detroit, MI 48202, USA.
Fernández de Henestrosa
A R
AR
Bhagwat
A S
AS
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D045647:DNA Glycosylases; D004260:DNA Repair; D004926:Escherichia coli / Q000201:enzymology* / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D044502:Thymine DNA Glycosylase; D051981:Uracil-DNA Glycosidase
D001426:Bacterial Proteins; D003470:Culture Media; D012333:RNA, Messenger; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D044502:Thymine DNA Glycosylase; D051981:Uracil-DNA Glycosidase; C113921:mismatch-specific thymine uracil-DNA glycosylase