Location

University of Nevada Las Vegas, Student Union Ball Room

Start Date

6-8-2009 9:30 AM

End Date

6-8-2009 12:00 PM

Description

While under conditions of stress, non-dividing cells may acquire beneficial mutations. This is referred to as stationary phase mutagenesis, or adaptive mutagenesis. Previous research has shown that actively transcribed genes and those under selective pressure are prone to mutations that confer escape from non-dividing conditions. Accordingly, strains lacking transcription factors have shown a drastically lower number of mutations that confer escape while under amino acid starvation than those observed in the wildtype background. Also, error-prone DNA polymerases are known to be active in cells under stress and it has been shown that strains lacking an error-prone DNA polymerase display reduced levels of stationary phase mutagenesis. It is possible to speculate that when active transcription stalls, perhaps due to pre-mutagenic lesions in the template DNA strand, error-prone polymerases are recruited to the site of stalled transcription as part of DNA repair processes. This interaction between transcription and DNA repair is likely to bias the accumulation of mutations at highly transcribed loci. This model may be tested with strains carrying deficiencies in Mfd (transcription factor), YqjH (error-prone DNA polymerase), or both. We expect the double-knockout strain to show a similar level of mutagenesis to those observed in strains carrying only one deficiency, and lower levels compared to those in the wildtype. Alternatively, if these factors influence mutation separately, a double-knockout should show even lower accumulation of adaptive mutants than either the Mfd- or YqjH-. We are currently constructing the double-knockout strain in Bacillus subtilis.

Keywords

Bacillus subtilis; Cell mutations; Cell stress; Gene mutations; Mutagenesis; Non-dividing cells

Disciplines

Cell Biology | Genetics

Language

English

Comments

Abstract & poster


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Aug 6th, 9:30 AM Aug 6th, 12:00 PM

Stationary phase mutagenesis in Bacillus subtilis: The interaction between transcription and error-prone replication in conditions of stress

University of Nevada Las Vegas, Student Union Ball Room

While under conditions of stress, non-dividing cells may acquire beneficial mutations. This is referred to as stationary phase mutagenesis, or adaptive mutagenesis. Previous research has shown that actively transcribed genes and those under selective pressure are prone to mutations that confer escape from non-dividing conditions. Accordingly, strains lacking transcription factors have shown a drastically lower number of mutations that confer escape while under amino acid starvation than those observed in the wildtype background. Also, error-prone DNA polymerases are known to be active in cells under stress and it has been shown that strains lacking an error-prone DNA polymerase display reduced levels of stationary phase mutagenesis. It is possible to speculate that when active transcription stalls, perhaps due to pre-mutagenic lesions in the template DNA strand, error-prone polymerases are recruited to the site of stalled transcription as part of DNA repair processes. This interaction between transcription and DNA repair is likely to bias the accumulation of mutations at highly transcribed loci. This model may be tested with strains carrying deficiencies in Mfd (transcription factor), YqjH (error-prone DNA polymerase), or both. We expect the double-knockout strain to show a similar level of mutagenesis to those observed in strains carrying only one deficiency, and lower levels compared to those in the wildtype. Alternatively, if these factors influence mutation separately, a double-knockout should show even lower accumulation of adaptive mutants than either the Mfd- or YqjH-. We are currently constructing the double-knockout strain in Bacillus subtilis.