Edwin Antony, PhD

Bio

Edwin AntonyI grew up in southern India and graduated from Loyola College with a B.Sc. in zoology and chemistry. I then received a M.Sc. in biochemistry from St. Joseph’s College. After arriving in the United States in 2000, I received my Ph.D. from Wesleyan University in 2005. My dissertation work uncovered the coupling between ATP binding/hydrolysis and mismatch recognition by prokaryotic MutS and eukaryotic Msh2-Msh6 complexes. After a year of postdoctoral training investigating voltage-gated calcium channel with Dr. David Yue at John’s Hopkins University, I returned to working with DNA repair alongside Dr. Tom Ellenberger and Dr. Tim Lohman at Washington University in St. Louis. My major findings centered around the Srs2 helicase and the mechanism of Rad51 filament disassembly. In my independent career since 2012, my team has uncovered the complexities underlying the mechanism of action of replication protein A (RPA), Rad52, and several other enzyme complexes. We utilize a comprehensive experimental toolkit that includes structural, biophysical, single-molecule and cellular approaches to arrive at quantitative understanding of biomolecular processes.

Research

The Antony group investigates the underlying molecular principles of how protein complexes function together to protect genomic integrity. Our perspective centers around Replication Protein A (RPA), a single-strand DNA binding protein that coats the DNA during various DNA metabolic processes including replication, repair, recombination, and DNA repair. In addition to binding to DNA, it recruits or functions alongside more than three dozen DNA metabolic proteins. How RPA imparts functional specificity to these various processes remains a mystery. Recent work from the group has uncovered: 1) How the various domains of RPA are utilized during homologous recombination. 2) How RPA and Rad52 function together to promote Rad51 filament formation. 3) Developed new fluorescence tools to interrogate how helicases work on RPA-coated DNA during replication and repair. 4) A new Aurora kinase-RPA signaling axis that regulates events during chromosome segregation in mitosis. New areas of research explore targeting RPA through small molecule inhibitors and investigating the roles of multi-domain RNA binding proteins in genomic stability.

Website: www.antonylab.org

Recent publications

  1. Roshan P., Kuppa S., Mattice J., Kaushik V., Chadda R., Pokhrel N., Tumala B., Bothner B., Antony E., and Origanti S. An Aurora B-RPA signaling axis secures chromosome segregation fidelity. bioRxiv: doi: https://doi.org/10.1101/2022.09.26.509563
  2. Kuppa S., Deveryshetty J., Chadda R., Mattice J., Pokhrel H., Kaushik V., Patterson A., Dhingra N., Pangeni S., Sadauskas M.K., Shiekh S., Balci H., Ha T., Zhao X., Bothner B., and Antony E. Rtt105 configurationally staples RPA and blocks facilitated exchange and interactions with RPA-interacting proteins. Nature Communications. 2022. 13(1):5152.
  3. Hormeno S, Wilkinson O.J.,  Aicart-Ramos C., Kuppa S., Antony E. , Dillingham M.S., and Moreno-Herrero F. Human HELB is a processive motor protein which catalyses RPA clearance from single-stranded DNA. Proc Natl Acad Sci U S A. 2022  12;119(15):e2112376119.
  4. Dhingra, N., Kuppa, S., Wei, L., Pokhrel, N., Baburyan, S., Meng, X., Antony, E., and Zhao, X. The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin. Proc Natl Acad Sci U S A. 2021. 119(15):e2112376119.
  5. Ahmad, F., Patterson, A., Deveryshetty, J., Mattice, J., Pokhrel, N., Bothner,  B., and Antony, E. Hydrogen-deuterium exchange reveals a dynamic DNA binding map of Replication Protein A. Nucleic Acids Research. 2021. 49(3):1455-1469.
  6. Pokhrel N., Caldwell, C.C., Corless, E.I., Tillison, E.A., Tibbs, J., Jocic, N., Ali Tabei, S.M., Wold, M.S., Spies, M. and Antony E. Dynamics and Selective Remodeling of the DNA Binding Domains of RPA. Nature Structural & Molecular Biology. 26, p129–136 (2019).
  7. Yates LA, Aramayo RJ, Pokhrel N, Caldwell CC, Kaplan JA, Perera RL, Spies M, Antony E, and Zhang X. A structural and dynamic model for the assembly of Replication Protein A on single stranded DNA. Nature Communications. 2018.