Medical Sciences Commons^™

Formation Of Complex And Unstable Chromosomal Translocations In Yeast, Kristina H. Schmidt, Emilie Viebranz, Lillian Doerfler, Christina Lester, Aaron Rubenstein

Molecular Biosciences Faculty Publications

Genome instability, associated with chromosome breakage syndromes and most human cancers, is still poorly understood. In the yeast Saccharomyces cerevisiae, numerous genes with roles in the preservation of genome integrity have been identified. DNA-damage-checkpoint-deficient yeast cells that lack Sgs1, a RecQ-like DNA helicase related to the human Bloom's-syndrome-associated helicase BLM, show an increased rate of genome instability, and we have previously shown that they accumulate recurring chromosomal translocations between three similar genes, CAN1, LYP1 and ALP1. Here, the chromosomal location, copy number and sequence similarity of the translocation targets ALP1 and LYP1 were altered to gain insight into the …

Epistatic Relationships Between Sara And Agr In Staphylococcus Aureus Biofilm Formation, Karen E. Beenken, Lara N. Mrak, Linda M. Griffin, Agnieszka K. Zielinska, Lindsey N. Shaw, Kelly C. Rice, Alexander R. Horswill, Kenneth W. Bayles, Mark S. Smeltzer

Molecular Biosciences Faculty Publications

Background: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeutically relevant in that mutation of agr results in increased biofilm formation and decreased antibiotic susceptibility while mutation of sarA has the opposite effect. To the extent that induction of agr or inhibition of sarA could potentially be used to limit biofilm formation, this makes it important to understand the epistatic relationships between these two loci.

Methodology/Principal Findings: We generated isogenic sarA and agr mutants in clinical isolates of S. …

Identification And Characterization Of Sigma(S), A Novel Component Of The Staphylococcus Aureus Stress And Virulence Responses, Lindsey N. Shaw, Catharina Lindholm, Tomasz K. Prajsnar, Halie K. Miller, Melanie C. Brown, Ewa Golonka, George C. Stewart, Andrej Tarkowski, Jan Potempa

Molecular Biosciences Faculty Publications

S. aureus is a highly successful pathogen that is speculated to be the most common cause of human disease. The progression of disease in S. aureus is subject to multi-factorial regulation, in response to the environments encountered during growth. This adaptive nature is thought to be central to pathogenesis, and is the result of multiple regulatory mechanisms employed in gene regulation. In this work we describe the existence of a novel S. aureus regulator, an as yet uncharacterized ECF-sigma factor (sigma(S)), that appears to be an important component of the stress and pathogenic responses of this organism. Using biochemical approaches …

Factors Contributing To The Biofilm-Deficient Phenotype Of Staphylococcus Aureus Sara Mutants, Laura H. Tsang, James E. Cassat, Lindsey N. Shaw, Karen E. Beenken, Mark S. Smeltzer

Molecular Biosciences Faculty Publications

Mutation of sarA in Staphylococcus aureus results in a reduced capacity to form a biofilm, but the mechanistic basis for this remains unknown. Previous transcriptional profiling experiments identified a number of genes that are differentially expressed both in a biofilm and in a sarA mutant. This included genes involved in acid tolerance and the production of nucleolytic and proteolytic exoenzymes. Based on this we generated mutations in alsSD, nuc and sspA in the S. aureus clinical isolate UAMS-1 and its isogenic sarA mutant and assessed the impact on biofilm formation. Because expression of alsSD was increased in a biofilm but …