wang dot jue at gmail dot com
Before this, I studied physics at McGill University in Canada.
All organisms must faithfully replicate their DNA to minimize errors that could lead to cell death or decreased fitness. How do cells avoid mistakes during DNA replication? How is DNA replication coordinated with cellular processes such as growth and division? How is replication responsive to external cues such as nutrient availability? These are important unresolved questions which my lab will address using the Gram-positive bacterium Bacillus subtilis. B. subtilis has a simpler mode of replication compared to eukaryotes, and is amenable to genetic, genomic, quantitative and systematic analyses. Understanding universal principles of regulating DNA replication helps us to understand causes of genetic diseases and cancer.
I have employed genomic microarray techniques and characterized a novel mechanism for regulation of replication elongation by nutrient availability in B. subtilis. Upon amino acid starvation, the small nucleotides (p)ppGpp rapidly and directly inhibit B. subtilis primase, an essential component of the replication machinery. Regulation of elongation could potentially limit DNA damage caused by uncontrolled replication under unfavorable environments, and help to maintain genomic stability. My lab will combine genetics and biochemistry to elucidate the molecular mechanism of this inhibition. We will also examine whether this regulation might help to minimize disruption to replication forks, by monitoring the survival, mutation, and DNA damage response of cells when this regulation is abolished. In addition, we will investigate the state of arrested replication forks in the middle of a chromosome and the events that lead to replication restart.
Finally, the organization of bacterial genomes helps to reduce problems of replication. The majority of genes in bacterial genomes co-orient with replication and I found that this co-orientation bias of transcription and replication promote smooth replication fork progression on a genomic scale. My lab will use genomic and genetic approaches to further examine the nature of the selective pressure that lead to the evolution of co-orientation.
Wang, J.D., Berkmen, M.B., Grossman, A.D. Genome-wide co-orientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis. submitted.
Wang, J.D., Sanders G.M., Grossman, A.D. Nutritional control of elongation of DNA replication by (p)ppGpp. submitted.
Goranov, A.I., Kuester-Schoeck, E., Wang, J.D., Grossman, A.D. (2006) Characterization of the global transcriptional responses to different types of DNA damage and disruption of replication in Bacillus subtilis. J. Bacteriol. 188(15):5595-605.
Wang, J.D., Rokop, M.E., Barker, M.M., Hanson, N.R., Grossman, A.D. (2004) Multicopy plasmids affect replisome positioning in Bacillus subtilis. J. Bacteriol. 186(21):7084-90.
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