Ph.D., Biochemistry, Molecular and Cell Biology, Cornell University, 1995.
B.S., Biological Sciences, University of California, Irvine, 1983.
Biochemistry
Biochemistry Laboratory
Advanced Topics in Biochemistry
My laboratory is interested in cellular responses to DNA damage and the biochemistry of DNA repair. Cells encounter DNA damaging agents continually. Sources of DNA damage can be manmade (tobacco smoke, environmental pollutants, etc.) or natural (reactive oxygen metabolites, ultraviolet light from the sun, etc.). Normal cells are capable of repairing damage to their DNA as a means of preventing mutation. We wish to learn more about this process, which represents a vital natural defense against cancer. One of our projects is the investigation of interactions between repair endonucleases, which remove damaged DNA, and proliferating cell nuclear antigen (PCNA), which helps to synthesize new (undamaged) DNA at the repair site. Other kinds of proteins can also bind to PCNA, including mismatch recognition complexes (such as MSH2-MSH6) and cell cycle regulatory proteins (such as p21, a cyclin-dependent kinase inhibitor that is made in response to DNA damage). A major goal of the laboratory is to learn how these regulatory and repair proteins work together as part of an integrated cellular response to DNA damage. A second project examines the function and regulation of the human tumor suppressor p53. When DNA damage occurs, p53 coordinates a variety of protective responses, including transient cell cycle arrest and apoptosis. Another area of interest is the study of intracellular activities of Ap4A-family dinucleotide signaling molecules. These second messenger molecules are produced in response to certain types of DNA damage and cellular stress, and misregulation of this response may play a role in the development of some types of environmentally-induced cancers.
PCNA subunits (magenta, gray, brown)
form a trimer that can encircle DNA (image adapted from PDB 1AXC, deposited
by Gulbis & Kuriyan). PCNA-binding peptides (yellow, gold, green)
make a tight complex with PCNA. An expanded view of the p21 peptide is
shown with selected H-bond conformational constraints (modeled with InsightII
using Nevada BRIN Structural Bioinformatics Core workstation). |
Nevada INBRE Research Project "Senescence Signaling Through p53"
| *Selected for the cover illustration of the July 2007 issue of JPET |  |
Gary, RK, and Jensen, DA. (2005). The p53 inhibitor pifithrin-alpha forms a sparingly soluble derivative via intramolecular cyclization under physiological conditions. Mol. Pharm. 2: 462-474.
Sharma, S, Sommers, JA, Gary, RK, Friedrich-Heineken, E, Hubscher, U, and Brosh Jr, RM. (2005). The interaction site of flap endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic Acids Res. 33: 6769-6781.
Gary, RK, and Kindell, SM. (2005). Quantitative assay of senescence-associated beta-galactosidase activity in mammalian cell extracts. Analytical Biochem. 343: 329-334.
Gary, RK. (2004). The concentration-dependence of the delta-S term in the Gibbs free energy function: Application to reversible reactions in biochemistry. J. Chem. Educ. 81: 1599-1604.
Ramanathan K, Gary RK, Apostol A, and Rogers KR. (2003). A fluorescence-based assay for DNA damage induced by radiation, chemical mutagens and enzymes. Curr. Appl. Phys. 3: 99-106.
Lehnert, NM, Gary, RK, Marrone, BL, and Lehnert, BE. (2001). Inhibition of normal human lung fibroblast growth by beryllium. Toxicology 160: 119-127.
Clark, AB, Valle, F, Drotschmann, K, Gary, RK, and Kunkel, TA. (2000). Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes. J. Biol. Chem. 275: 36498-36501.
Matsumoto, Y, Kim, K, Hurwitz, J, Gary, R, Levin, DS, Tomkinson, AE, and Park, MS. (1999). Reconstitution of proliferating cell nuclear antigen-dependent repair of apurinic/apyrimidinic sites with purified human proteins. J. Biol. Chem. 274: 33703-33708.
Gary, R, Park, MS, Nolan, JP, Cornelius, HL, Kozyreva, OG, Tran, HT, Lobachev, KS, Resnick, MA, and Gordenin, DA. (1999). A novel role in DNA metabolism for the binding of Fen1/Rad27 to PCNA and implications for genetic risk. Mol. Cell. Biol. 19: 5373-5382.
Gary, R, Kim, K, Cornelius, HL, Park, MS, and Matsumoto, Y. (1999). PCNA facilitates excision in long-patch base excision repair. J. Biol. Chem. 274: 4354-4363.
Montecucco, A, Rossi, R, Levin, DS, Gary, R, Park, MS, Motycka, TA, Ciarrocchi, G,Villa, A, Biamonti, G, and Tomkinson, AE. (1998). DNA ligase I is recruited to sites of DNA replication by an interaction with proliferating cell nuclear antigen: identification of a common targeting mechanism for the assembly of replication factories. EMBO J. 17: 3786-3795.
Gary, R, Ludwig, DL, Cornelius, HL, MacInnes, MA, and Park, MS. (1997). The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21. J. Biol. Chem. 272: 24522-24529.
Gary, R, and Bretscher, A. (1995). Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site. Mol. Biol. Cell 6: 1061-1075.
Bretscher, A, Gary, R, and Berryman, M. (1995). Soluble ezrin purified from placenta exists as stable monomers and elongated dimers with masked C-terminal ezrin-radixin-moesin association domains. Biochemistry 34: 16830-16837.
Berryman, M, Gary, R, and Bretscher, A. (1995). Ezrin oligomers are major cytoskeletal components of placental microvilli: A proposal for their involvement in cortical morphogenesis. J. Cell Biol. 131: 1231-1242.
Gary, R, and Bretscher, A. (1993). Heterotypic and homotypic associations between ezrin and moesin, two putative membrane-cytoskeletal linking proteins. Proc. Natl. Acad. Sci. USA 90: 10846-10850.
Franck, Z, Gary, R, and Bretscher, A. (1993). Moesin, like ezrin, colocalizes with actin in the
cortical cytoskeleton in cultured cells, but its expression is more variable. J. Cell Sci. 105:
219-231.
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Lab Group (Summer 2007): Priyatham Gorjala, Diane Tay, Ron Gary, and Swapna Mudireddy (from left). |
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| Lab Group (Spring 2003): Ron Gary, Diana Musngi, Derek Jensen, Christian Agyei, Shannon Coates, and Casey Hall (from left). |
Last updated 08-22-07.
