Assistant Professor, Departments of Molecular and Human Genetics and Biochemistry & Molecular Biology; Program in Cell & Molecular Biology

B.Sc., McGill University, Canada, 1995
Ph.D., University of California at San Francisco, 2002
Postdoc, MIT, 2006

RESEARCH INTERESTS:

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 promotes 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 leads to the evolution of co-orientation.

SELECTED PUBLICATIONS:

1. Srivatsan A**, Yi H**, Peng J, Tehranchi AK, Gibbs R, Wang JD*, Chen R* (2008). High precision whole-genome sequencing of laboratory strains facilitates genetic studies. PLoS Genet. 4: e1000139. (*Corresponding authors) (**Equal contribution)

2. Srivatsan A, Wang JD (2008). Control of bacterial transcription, translation and replication by (p)ppGpp. Curr. Opin. Microbiol. 11: 100-105.

3. Wang JD, Sanders GM, Grossman AD (2007). Nutritional control of elongation of DNA replication by (p)ppGpp. Cell 128: 865-875.

4. Wang JD, Berkmen MB, Grossman AD (2007). Genome-wide co-orientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis. Proc. Natl. Acad. Sci. USA 104: 5608-5613.

5. Goranov AI, Kuester-Schoeck E, Wang JD, Grossman AD (2006). Characterization of the global transcriptional responses to different types of DNA damage and disruption of replication in Bacillus subtilis. J. Bacteriol. 188: 5595-5605.

6. Wang JD, Rokop ME, Barker MM, Hanson NR, Grossman AD (2004). Multicopy plasmids affect replisome positioning in Bacillus subtilis. J. Bacteriol. 186: 7084-7090.

7. Wang JD, Herman C, Tipton KA, Gross CA, Weissman JS (2002). Directed evolution of substrate-optimized GroEL/S chaperonins. Cell 111: 1027-1039.

8. Wang JD, Weissman JS (1999). Thinking outside the box: new insights into the mechanism of GroEL-mediated protein folding. Nat. Struct. Biol. 6: 597-600.

9. Wang JD, Michelitsch MD, Weissman JS (1998). GroEL-GroES-mediated protein folding requires an intact central cavity. Proc. Natl. Acad. Sci. USA 95: 12163-12168.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Jue D. Wang, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, Rm. S-911
Houston, Texas 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-8182
Fax: 713-798-8142
E-mail:

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