Alexandra Deaconescu, B.E., Ph.D.Edit My Page
Research in my laboratory focuses on the biochemical and biophysical underpinnings of DNA transactions essential for the maintenance of genomes and for controlling the flow of genetic information. Our approach combines biochemistry and biophysics with complementary structure determination methods (X-ray crystallography, small-angle X-ray scattering and electron microscopy) with the goal of elucidating the architecture, function, and regulation of protein and protein-nucleic acid complexes.
Dr. Deaconescu received her undergraduate degree in chemical engineering from The Cooper Union for the Advancement of Science and Art in 2001, and then completed doctoral work in molecular biophysics at The Rockefeller University. Between 2006-2013, Dr. Deaconescu conducted postdoctoral research at Brandeis University and the HHMI Janelia Farm Research Campus in the laboratory of Dr. Nikolaus Grigorieff. Her work brought structural and mechanistic insight into the processes of transcription-coupled DNA repair and cytoskeleton regulation. She will join the Molecular Biology, Cell Biology and Biochemistry Department at Brown University in January, 2014. Dr. Deaconescu welcomes applications from undergraduates and postgraduates of diverse backgrounds and interests for work on a variety of exciting research projects.
The double-helical nature of DNA, the length of genes, and the ubiquitous presence of endogenous and exogenous DNA-damaging agents pose significant topological and information processing challenges to the cell. DNA serves as a track for a variety of essential cellular machines, including the DNA replication and transcription machineries that scan or read the chromosome. Our overall goal is to understand how DNA repair pathways interface with other cellular processes. To this end, we are focusing on a specialized subpathway of nucleotide excision repair (NER) called transcription-coupled DNA repair (TCR). TCR is triggered by the stalling of RNA polymerase molecules at certain DNA lesions, such as UV-induced damage. In TCR, as in NER, repair is achieved through a "cut and patch" mechanism, in which excision of a short oligonucleotide containing the DNA damage is followed by resynthesis and gap filling. Unlike in genome-wide NER, the initial recognition of the DNA damage is mediated by RNA polymerase itself (rather than dedicated repair machinery), which stalls and serves as a beacon for recruitment of transcription-repair coupling factors. These, in turn, remodel or dissociate RNA polymerase transcription complexes and preferentially recruit NER proteins to the damaged site.
TCR exists in both prokaryotes and eukaryotes, and, in humans, has been associated with a variety of syndromes, such as UV-sensitive syndrome, DeSantis Cacchione, and the better-known progeroid (accelerated-aging) Cockayne syndrome, characterized by severe, multi-systemic developmental and neurological defects. In ongoing experiments, we are dissecting the complicated mechanochemistry of transcription-repair coupling factors with the overall goal of understanding how these proteins, part of a large family of dsDNA translocases, utilize the energy of ATP hydrolysis to exert mechanical work to remodel their substrates and recruit NER proteins.
Selected Grants and Awards
2013 - Howard Hughes Medical Institute/Brandeis University Scholar Award in Quantitative Biology
2012 - W.M. Keck Postdoctoral Fellowship, The W.M. Keck Foundation and the Gulf Coast Research Consortium/Computational Cancer Biology Program (declined)
2010 - Scholarship, International School of Crystallography at Ettore Majorana Centre, Erice, Italy, A NATO Advanced Study Institute
2008-2010 - Damon Runyon Cancer Research Foundation Postdoctoral Fellowship
2008 - Fellowship, Japanese Ministry of Education, Culture, Sports, Science and Technology and International Brain Research Organization
2004 - "Rockefeller University Abroad" Prize, The Rockefeller University
2001- The Herbert B. Baldwin Prize for Excellence in Chemical Engineering
- Deaconescu, A.M.,# RNA polymerase between lesion bypass and DNA repair (2013) Cell. and Mol. Life Sci. (in press, # invited author)(2013)
- Deaconescu, A.M., Sevostyanova, A, Artsimovitch, I., Grigorieff, N., NER Machinery Recruitment by Transcription-Repair Coupling Factor Involves Unmasking of a Conserved Intramolecular Interface (2012) Proc. Natl. Acad. Sci. USA 109(9):3353-3358(2012)
- Deaconescu, A.M.,*,# Artsimovitch, I, Grigorieff, N. Interplay of DNA repair and transcription- from structures to mechanisms (2012) Trends Biochem. Sci. 37(12):543-52 (*corresponding author, # invited author)(2012)
- Szyk, A., Deaconescu, A.M., Piszczek, G., Roll-Mecak, A. Tubulin tyrosine ligase structure reveals adaptation of an ancient fold to bind and modify tubulin (2011) Nat Struct Mol Biol. 18(11):1250-1258(2011)
- Okada, K., Bartolini, F., Deaconescu, A.M., Moseley, J.B., Dogic, Z., Grigorieff, N., Gundersen, G.G., Goode, B.L. The tumor suppressor protein APC is a potent nucleator of actin assembly that synergizes with the formin mDia1 (2010) J Cell Biol 189:1087-96(2010)
- Deaconescu, A.M., Savery, N.J., Darst, S.A. The bacterial transcription-repair coupling factor (2007) Curr Opin Struct Biol. 1:96-102(2007)
- Deaconescu, A.M., Chambers, A.L., Smith A.J., Nickels, B.E., Hochschild, A., Savery, N.J., Darst, S.A. Structural Basis for Bacterial Transcription-Coupled DNA Repair (2006) Cell. 124(3): 507-520(2006)
- Deaconescu, A.M. and Darst, S.A. Crystallization and preliminary structure determination of Escherichia coli Mfd, the transcription-repair coupling factor (2005) Acta Cryst. F. F61: 1062-1064(2005)
- Deaconescu, A.M, Roll-Mecak, A., Bonanno, J.B., Kycia, H., Gerchman, S.E., Studier, W., and Burley, S.K. X-ray Structure of Saccharomyces cerevisiae Homologous Mitochondrial Matrix Factor Hmf1 (2002) Proteins. 48(2): 431-6(2002)