Patricia Kane, PhD
Chair and Professor
The central goals of scientists in the Biochemistry and Molecular Biology department are to research fundamental mechanisms in cells and organisms at the molecular level and to train the next generation of scientists. Read More...
Faculty Research Interests
Wenyi Feng, PhD
- Associate Professor of Biochemistry and Molecular Biology
Research Programs and Affiliations
- Biochemistry and Molecular Biology
- Biomedical Sciences Program
Education & Fellowships
- Postdoctoral Fellow: University of Washington, Seattle, WA, 2010
- PhD: University of Miami School of Medicine, 2002
Chromosomal DNA replication origins (location, timing and regulation), replication fork integrity and checkpoint regulation, genomic instability and chromosome fragility in both the yeast and human genome
Link to PubMed (Opens new window. Close the PubMed window to return to this page.)
How do defects in DNA replication lead to genomic instability? This question bears on our understanding of a wide spectrum of human diseases, including chromosome fragility, cancer, neurodegeneration, and even autoimmune disorders. Eukaryotic chromosomal DNA replication is a process that is at once robust and vulnerable. It is accurate and able to withstand environmental stress, such as DNA damage and replication impediments, through a highly evolved checkpoint mechanism. Yet the very act of replication, if executed in an untimely or uncoordinated fashion, can give rise to genomic instability.
My laboratory (http://fenglab-genomestabilityresearch.org) is interested in understanding the mechanisms of genomic instability induced by DNA replication stress. We are particularly interested in how cells protect the replication forks (junctions of replicated and unreplicated DNA) during replication stress by hydroxyurea (a drug that lowers cellular pools of deoxyribonucleotides). Unprotected replication forks due to mutations in the replication checkpoint genes can lead to single-stranded DNA (ssDNA) gaps in the genome and chromosome breakage. Yet the mechanisms through which these detriments of the genome occur are not well understood. We use the baker's yeast Saccharomyces cerevisiae as a model organism to study the mechanisms of the maintenance of replication fork integrity. We also apply the genomic mapping of ssDNA and chromosome breakage methods to reveal important landmarks such as origins of replication and chromosome fragile sites in the human genome.
The specific research projects in my laboratory are focused on addressing the following questions:
- What are the mechanisms of ssDNA production and chromosome fragility during replication stress?
- What structural changes accompany the destabilization of replication forks under replication stress?
- What genomic rearrangements occur in rare survivors of checkpoint mutants after replication stress?
- Where are the origins of replication in the human genome and are there differences in the selection and usage of origins in different cell types and at different developmental stages?
- Where are the chromosome fragile sites in the human genome and how do they relate to origin locations?
- Feng W. (2016) Mec1/ATR, the Program Manager of Nucleic Acids Inc. Genes (Basel). 8(1). pii: E10. doi: 10.3390/genes8010010. Review.
- Peng J, Feng W. (2016) Incision of damaged DNA in the presence of an impaired Smc5/6 complex imperils genome stability. Nucleic Acids Res. pii: gkw720. [Epub ahead of print]
- Hang LE, Peng J, Tan W, Szakal B, Menolfi D, Sheng Z, Lobachev K, Branzei D, Feng W, Zhao X. (2015) Rtt107 is a multi-functional scaffold supporting replication progression with partner SUMO and ubiquitin ligases. Mol Cell. 60:268-79.
- Hoffman EA, McCulley A, Haarer B, Arnak R, Feng W. (2015) Break-seq reveals hydroxyurea-induced chromosome fragility as a result of unscheduled conflict between DNA replication and transcription. Genome Res. 25:401-12.
- Peng J, M. K. Raghuraman, Feng W. (2014) Analysis of ssDNA gaps and DSBs in genetically unstable yeast cultures. Methods Mol Biol. 1170:501-15.
- Peng J, M. K. Raghuraman, Feng W. (2014) Analysis of replication timing using synchronized budding yeast cultures. Methods Mol Biol. 1170:477-99.
- McCulley A, Haarer B, Viggiano S, Karchin J, Feng W. (2014) Chemical suppression of defects in mitotic spindle assembly, redox control, and sterol biosynthesis by hydroxyurea. G3. 4(1):39-48.
- Feng W*, Di Rienzi S, Raghuraman M K, Brewer B J. (2011) Replication stress-induced chromosome breakage is correlated with replication fork progression and is preceded by single-stranded DNA formation. G3. 1(5):327-35. *Corresponding author.
- Feng W, Bachant J, Collingwood D, Raghuraman M K, Brewer B J. (2009) Centromere replication timing determines different forms of genomic instabilit in Saccharomyces cerevisiae checkpoint mutants during replication stress. Genetics. 183(4):1249-60.
- Feng W, Collingwood D, Boeck M E, Fox L, Alvino G, Fangman W L, Raghuraman M K, Brewer B J. (2006) Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication. Nature Cell Biol. 8(2):148-55.