Uncovering Mechanisms of RNA-driven Genomic Stability and Instability

Abstract
Does genetic information flow from RNA to DNA in a more general fashion than anticipated? Is the central dogma of molecular biology often reversed to let RNA repair DNA damage or even recode genes on chromosomes? My group discovered that RNA serves as template to repair DNA double-strand breaks (DSBs) in budding yeast. We found that transfer of genetic information from RNA to DNA occurs with an endogenous generic transcript, and is thus a more common mechanism than previously anticipated. Our results suggest that transcript RNA may have a significant role in genome stability and genome modification, much more prominent than previously anticipated.

DNA is heavily ‘contaminated’ with RNA! Our invention of the ribose-seq technique to map ribonucleotides (rNMPs) in genomic DNA has demonstrated that rNMPs are widespread but not randomly distributed in yeast nuclear and mitochondrial DNA. Ribose-seq provides a novel technology to uncover whether and how rNMPs in DNA affect genome integrity and are linked to human degenerative diseases, like cancer. In collaborative multidisciplinary study at the interface of chemistry, physics and molecular biology, we revealed that rNMPs in DNA alter DNA structure and elasticity in a way that is dependent on the sequence context. Because ribose-seq allows us to identify hotspots of rNMPs in any DNA, including DNA from diseased cells, characterization of rNMP hotspots may become important both for understanding how DNA properties are altered at these loci, and possibly for developing specific drugs that target these sites.

 

Biography
Francesca Storici was born in Trieste, Italy. She graduated in Biology from the University of Trieste. Her Ph.D. in Molecular Genetics was conferred by the International School for Advanced Studies (SISSA), in Trieste in 1998, and she conducted research at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Trieste. From 1999 to 2007 she was an NIH postdoctoral fellow in the Laboratory of Molecular Genetics under the guidance of Dr. Michael A. Resnick at the National Institute of Environmental and Health Sciences (NIEHS, NIH) in the Research Triangle Park of North Carolina, USA. In 2007 she was a Research Assistant Professor at the Gene Therapy Center of the University on North Carolina at Chapel Hill with Dr. R. Jude Samulski. Francesca joined the faculty of the School of Biological Sciences at Georgia Tech in 2007 and received the title of Distinguished Cancer Scientist of the Georgia Research Alliance. She is currently an associate professor in the School of Biological Sciences at Georgia Tech. Her research is on genome stability, DNA repair and gene targeting.

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Event Details

Date/Time:

  • Thursday, August 31, 2017
    11:00 am