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Alexander Mazin

Alexander Mazin, PhD

Professor


Department: Biochemistry & Molecular Biology

Education

  • PhD - Institute of Cytology and Genetics, The Russian Academy of Science (1984)

Dr. Mazin is a professor in the Department of Biochemistry & Molecular Biology at Drexel University College of Medicine.

Research Interests

Mechanisms of DNA double-stranded break repair in humans and in yeast; role of homologous recombination in tumorigenesis; functions of Rad5, Rad54, and Rad51 proteins

Research

Our studies focus on the mechanisms of homologous recombination in humans. The homologous recombination pathway is crucial for maintenance of genome stability. It promotes the repair of the most harmful DNA lesions: DNA double-stranded breaks and inter-strand cross-links. In addition, homologous recombination is important for faithful segregation of homologous chromosomes during meiosis. Deficiencies in homologous recombination lead to cancer, premature aging, and various chromosomal abnormalities such as Down, Klinefelter, and other syndromes. 

To achieve accurate repair of DNA double-stranded breaks the homologous recombination machinery uses homologous dsDNA as a template. The unique and evolutionary conserved mechanism of homologous recombination is responsible for recognition of homologous DNA sequences and their pairing. However, the molecular principles of this mechanism remain a mystery. To uncover these principles our lab investigates the biochemical activities of the key homologous recombination proteins including RAD51, its meiosis-specific homologue DMC1, RAD52, RAD54, and others. Using homologous recombination proteins we attempt to reconstitute the process DNA double strand break repair in vitro. 

Since the homologous recombination activity is vital for rapidly proliferating cells and may be protective against the killing effect of anti-cancer drugs, we are developing specific small-molecule inhibitors of key homologous recombination proteins. We will use these inhibitors for advancement of novel anti-cancer therapies.  In addition, these inhibitors can be used as a probe to analyze the functions of homologous recombination proteins in the cell.

In the Media

"Scientists Discover Way to Repair Broken DNA"
TrendinTech (June 16, 2017)

"Researchers Uncover New Instruction Manual to Repair Broken DNA"
(June 8, 2017)

"A Blueprint for Healing"
College of Medicine Alumni Magazine (Fall/Winter 2016)

Publications

"RAD54 N-terminal domain is a DNA sensor that couples ATP hydrolysis with branch migration of Holliday junctions"
Goyal N, Rossi MJ, Mazina OM, Chi Y, Moritz RL, Clurman BE, Mazin AV
Nature Comm., 9, article number 34, PMCID: PMC5750232 (2018)

"Rad52-inverse strand exchange drives RNA-templated DNA double-strand break repair"
Mazina OM, Keskin H, Nahamshet K, and Storici F, Mazin AV
Molecular Cell, 67(1), p 19-29 3e. PMCID: PMC5547995 (2017)

"Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors"
Huang F, Goyal N, Sullivan K, Hanamshet K, Patel M, Mazina OM, Wang CX, An WF, Spoonamore J, Metkar S, Emmitte KA, Cocklin S, Skorski T, Mazin AV
Nucleic Acids Res. 44, 4189-99 (2016)

"Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination"
Hanamshet K, OM Mazina and AV Mazin
Genes (Basel) 7(9): p. 63-81 (2016)

"HOP2-MND1 modulates RAD51 binding to nucleotides and DNA"
Bugreev DV, Huang F, Mazina OM, Pezza RJ, Voloshin ON, Daniel Camerini-Otero R, and Mazin AV
Nature Commun 5, 4198 (2014)

"Analysis of the activities of RAD54, a SWI2/SNF2 protein, using a specific small-molecule inhibitor"
Deakyne JS, Huang F, Negri J, Tolliday N, Cocklin S, and Mazin AV
J. Biol. Chem. 288, 31567-31580 (2013)

"Polarity and bypass of DNA heterology during branch migration of Holliday junctions by human RAD54, BLM, and RECQ1"
Mazina OM, Rossi MJ, Deakyne JS, Huang F, and Mazin AV
J. Biol. Chem. 287, 11820-11832 (2012)

"The RecA/RAD51 protein drives migration of Holliday junctions via polymerization on DNA. "
Rossi MJ, Mazina OM, Bugreev DV, and Mazin AV
Proc Natl Acad Sci USA 108, 6432-6437 (2011)

"Rad54, the motor of homologous recombination"
Mazin AV, Mazina OM, Bugreev DV, Rossi MJ
DNA Repair (Amst) 9:286-302 (2010)

"Human Rad54 protein stimulates human Mus81/Eme1 endonuclease"
Mazina OM, Mazin AV
Proc. Natl. Acad. Sci. USA, 105(47): p. 18249-18254 (2008)

"Novel pro- and anti-recombination activities of the Bloom's syndrome helicase"
Bugreev DV, Yu X, Egelman EH, Mazin AV
Genes & Development, 21: 3085-3094 (2007)

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

"Rad54 protein promotes branch migration of the Holliday junctions"
Bugreev DV, Mazina OM, and Mazin AV
Nature (London). 442: 590-593 (2006) Reviewed by Faculty of 1000 Biology

"Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity"
Bugreev DV, and Mazin AV
Proc. Natl. Acad. Sci. USA, 101: 9988-9993 (2004)


Contact Information


Research Office

Department of Biochemistry & Molecular Biology
245 North 15th Street
Mail Stop 497
Philadelphia, PA 19102
Phone: 215.762.7195
Fax: 215.762.4452