About

Yuh-Hwa Wang is a Professor of Biochemistry and Molecular Genetics at the University of Virginia School of Medicine. She holds a PhD from North Carolina State University. Her research focuses on understanding the structure and function of unusual DNA sequences in living cells, particularly how these sequences cause genome instability and lead to human diseases. Her work has significant implications for understanding chromosomal fragile sites, which are correlated with chromosomal deletions and gene rearrangements found in many cancers. She investigates the genesis of breakpoints at fragile sites during oncogenesis, examining chromatin structure, DNA replication, cell cycle checkpoints, and mechanisms of gene rearrangements such as RET/PTC. Additionally, her research explores trinucleotide repeat expansion diseases, analyzing the role of chromatin and DNA structure in disease pathology and repeat expansion mechanisms. Her laboratory provides training in chromatin biology, DNA repair, cell culture, molecular biology techniques, cytogenetics, and electron microscopy.

Research topics

• Biology
• Genetics
• Molecular biology
• Chemistry
• Biophysics

Selected publications

• Pausing sites of RNA polymerase II on actively transcribed genes are enriched in DNA double-stranded breaks

  Journal of Biological Chemistry · 2020 · 38 citations

  • Biology
  • Molecular biology
  • Genetics

  DNA double-stranded breaks (DSBs) are strongly associated with active transcription, and promoter-proximal pausing of RNA polymerase II (Pol II) is a critical step in transcriptional regulation. Mapping the distribution of DSBs along actively expressed genes and identifying the location of DSBs relative to pausing sites can provide mechanistic insights into transcriptional regulation. Using genome-wide DNA break mapping/sequencing techniques at single-nucleotide resolution in human cells, we found that DSBs are preferentially located around transcription start sites of highly transcribed and paused genes and that Pol II promoter-proximal pausing sites are enriched in DSBs. We observed that DSB frequency at pausing sites increases as the strength of pausing increases, regardless of whether the pausing sites are near or far from annotated transcription start sites. Inhibition of topoisomerase I and II by camptothecin and etoposide treatment, respectively, increased DSBs at the pausing sites as the concentrations of drugs increased, demonstrating the involvement of topoisomerases in DSB generation at the pausing sites. DNA breaks generated by topoisomerases are short-lived because of the religation activity of these enzymes, which these drugs inhibit; therefore, the observation of increased DSBs with increasing drug doses at pausing sites indicated active recruitment of topoisomerases to these sites. Furthermore, the enrichment and locations of DSBs at pausing sites were shared among different cell types, suggesting that Pol II promoter-proximal pausing is a common regulatory mechanism. Our findings support a model in which topoisomerases participate in Pol II promoter-proximal pausing and indicated that DSBs at pausing sites contribute to transcriptional activation.

  DOI

Recent grants

• NIH Grant R01CA085826

  NIH · $2.0M · 2011

• Genome-wide DNA Secondary Structure Analysis to Investigate DNA Fragility

  NIH · $2.8M · 2013–2025

• The Role of Fragile Sites in RET/PTC Rearrangement

  NIH · $2.5M · 2005–2021

Frequent coauthors

• Jack D. Griffith

  University of North Carolina at Chapel Hill

  40 shared

• Emmanuelle Delagoutte

  Inserm

  9 shared

• Thomas R. Cech

  University of Colorado Boulder

  9 shared

• Bengt Nordén

  Chalmers University of Technology

  9 shared

• Felicia L. Murphy

  University of Colorado Boulder

  9 shared

• David S. Hsu

  Beckman Research Institute

  9 shared

• Elisabeth Bertrand-Burggraf

  Centre National de la Recherche Scientifique

  9 shared

• Aziz Sancar

  University of North Carolina at Chapel Hill

  9 shared

Similar researchers at University of Virginia

• Stephen S. Richh-170
• Gary Owensh-107
• Jarrod Martoh-101
• Jennifer L. Westh-93
• Edward H. Egelmanh-93