Associate Professor of Biochemistry
Telephone: 215-762-7195
Alexander.Mazin@Drexelmed.edu

Education:
PhD (1984) Institute of Cytology & Genetics
The Russian Academy of Sciences
Postdoc (1994-1999) University of California, Davis
 
Research Program

Research is focused on the study of homologous recombination (HR) in human cells. DNA damage may give rise to mutations that lead to premature aging, cancer and other genetic diseases. Homologous recombination (HR) is a very important cellular system that repairs damaged DNA; it deals with potentially lethal lesions, i.e. DNA double-stranded breaks (DSB) and inter-strand cross-links. To repair damaged DNA the HR system uses a homologous dsDNA as a template. This mechanism includes recognition of two homologous DNA sequences, their pairing, and exchange of DNA strands between homologous partners. Due to this unique and evolutionary conserved mechanism, HR corrects damaged DNA, generally, error-free, operating preferentially in actively proliferating cells, i.e. embryonic stem cells and generative cells, where no errors can be tolerated.

Recently, the major components of the human HR system have been identified. They include Rad51 protein and its six paralogs: Xrcc2, Xrcc3, Rad51B, Rad51C, Rad51D, and a meiosis-specific homologue, Dmc1. Rad51 protein binds ssDNA and forms a helical nucleoprotein filament that promotes DNA strand exchange reaction and also provides an interface for interaction with other HR proteins, i.e. Rad52 and Rad54. Our laboratory is pursuing two experimental lines. Along the first line, we have been determining the contribution of each individual protein of HR to the mechanism of repair of DSB in mammalian cells. For this purpose we are purifying these proteins and reconstructing the HR system in vitro. Along the second line, using in vitro assays we have been searching for HR anomalies (hypo- and hyperactivity) in malignant cells. Since the HR activity is vital for rapidly proliferating cells and may be protective against the killing effect of anti-cancer drugs, we plan to expand this line by screening for specific inhibitors of HR proteins, which may have an anti-cancer potential.

Selected Publications

Bugreev, D.V., Yu, X., Egelman, E.H., Mazin, A.V. (2007). Novel pro- and anti-recombination activities of the Bloom’s syndrome helicase. Genes & Development, in press.

Bugreev, D.V., Mazin, A.V. (2007) Reconstitution of DNA double-stranded breaks in vitro. Nature Protocols, published online 2 August 2007 (doi: 2010.1038/nprot.2007.2342).

Mazina, O. M., Rossi, M. J., Thoma, N., and Mazin A. V. (2007). Interactions of human Rad54 protein with branched DNA molecules. J. Biol. Chem., 282 (29): 21068-21080.

Bugreev, D. V., Hanaoka, F., and Mazin, A. V. (2007). Rad54 dissociates homologous recombination intermediates by branch migration. Nature Struct. & Mol. Biol., 14 (8): 746-753.

Bugreev, D. V., Mazina, O.M., and Mazin, A. V. (2006). Analysis of branch migration activities of proteins using synthetic DNA substrates. Nature Protocols., published online 1 September 2006 (doi:2010.1038/nprot.2006.2217).

Bugreev, D. V., Mazina, O.M., and Mazin, A. V. (2006). Rad54 protein promotes branch migration of the Holliday junctions. Nature (London). v. 442: 590-593. Selected by Faculty of 1000 Biology.

Thoma, N. H., Czyzewski, B. K., Alexeev, A. A., Mazin, A. V., Kowalczykowski, S. C., Pavletich, N.P. (2005). Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. Nature Struct. & Mol. Biol., v. 12:350-356.

Bugreev, D V., Golub, E I, Stasiak, A Z, Stasiak, A, and A, Mazin A V. (2005). Activation of human meiosis-specific recombinase Dmc1 by Ca2+. J. Biol. Chem.  280 (29): p. 26886-95.

Mazina, O. M., Mazin, A. V., Nakagawa T., Kolodner R. D., and Kowalczykowski S. C. (2004).
Saccharomyces cerevisiae Mer3 helicase stimulates 3’-5’ heteroduplex extension by Rad51: Implications for crossover control in meiotic recombination. Cell, v.117:47-56.

Bugreev, D. V., and Mazin, A. V. (2004). Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity. Proc. Natl. Acad. Sci. USA, v.101: 9988-9993 (Track II).

Mazina, O. M., and Mazin, A. V. (2004). Human Rad54 protein stimulates DNA strand exchange activity of hRad51 protein in the presence of Ca2+. J. Biol. Chem., v. 279: 52041-52051. Selected by the JBC editors as a Paper of the Week (top 1-2% of JBC papers).