Associate Professor of Biochemistry
Carver College of Medicine
University of Iowa
51 Newton Rd., 4-532 BSB
Iowa City, IA 52242
Lab Phone: +1-319-335-3223
June 1994 B.S., Physics/Biophysics
St. Petersburg State Polytechnic University, St. Petersburg, Russia
April 1996 M.S., Physics/Biophysics
St. Petersburg State Polytechnic University, St. Petersburg, Russia and
Petersburg Nuclear Physics Institute, Gatchina, St. Petersburg, Russia
March 2000 Ph.D., Biological Sciences
Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan
2000 – 2005 Postdoctoral training in single-molecule biophysics with Dr. Stephen C.
Kowalczykowski, University of California at Davis, Davis, CA, USA
Physical and single-molecule biochemistry of DNA Repair; molecular processes underlying maintenance of genetic integrity, genomic instability, cancer and aging; biophysical approaches aimed to discern biochemical mechanisms, regulation and function of DNA helicases and DNA-motor proteins; assembly and regulation of molecular machines involved in genome maintenance and DNA repair; mechanistic aspects of protein-nucleic acids interactions; homologous genetic recombination.
Mechanisms of homologous recombination
Work in my lab focuses on the molecular machines supporting genetic integrity, DNA recombination and repair. We combine biochemical, biophysical and single-molecule approaches to build a coherent mechanistic description of homologous genetic recombination, arguably the most enigmatic process in the DNA metabolism. The central step in recombination involves the search for the homology between two DNA molecules and the subsequent exchange of the DNA strands. In all organisms from bacteriophage to vertebrates and plants, this central step is orchestrated by the RecA/RAD51 family of the DNA strand exchange proteins (recombinases).
Our goal is to determine the universal mechanism of the DNA strand exchange reaction. The homologous recombination systems in modern organisms are complex and are inextricably interconnected with other genome maintenance processes. All modern RecA/RAD51 proteins are tightly regulated by the recombination mediators, antirecombinases and numerous posttranslational modifications. It is likely, however, that the ancestral RecA-like recombinases were “bare bones” and may provide a simpler system to investigate the recombination mechanisms. How the RecA homologs have evolved to accommodate the needs of different species and how have the paralogs evolved will bring about the fundamentally important insights in the mechanism of homologous recombination, a process essential for preserving the integrity of the genome and for the generation of genetic diversity. The molecular history of the RecA-like recombinases and paralogs will be probed though paleo-enzymology.
Our second goal is to define how RAD51/RecA family recombinases, recombination mediators, mismatch repair proteins and recombinational DNA helicases are integrated into the DNA repair and maintenance machines through a network of molecular associations and posttranslational modifications. The ultimate goal of our research is to go beyond deciphering the fundamental molecular mechanisms of the enzymes, proteins, and macromolecular ensembles orchestrating DNA repair to find an Achilles’ heel in their mechanism of action or malfunction. This will enable us to contribute to an emerging generation of targeted therapies aimed at attacking specific aspects of cancer and aging-related diseases.
- Bain, F.E, Wu, C.G., and Spies, M.‡, Single-molecule sorting of posttranslationally modified DNA helicases (2016) Methods, in press
- Chen, R., Subramanyam, S., Elcock, A.H., Spies, M., and Wold, M.S.‡, Dynamic binding of Replication Protein A is required for DNA repair (2016) NAR, in press [PMID: 26903512; PMCID: in progress]
- Boehm, E.M., Powers, K.T., Kondratick, C.M., Spies, M., Houtman, J.C., Washington, M.T.‡, The PCNA-Interacting Protein (PIP) Motif of DNA Polymerase η Mediates its Interaction with the C-Terminal Domain of Rev1 (2016) JBC in press [PMID: 26903512; PMCID: in progress]
- Spies, M.‡ and Fishel, R.‡, Mismatch Repair During Homologous and Homeologous Recombination (2015) Cold Spring Harbor Perspectives in Biology March 2015;7:a022657 [PMID: 25731766; PMCID: in progress]
- Ghoneim, M. and Spies, M.‡, Direct Correlation of DNA Binding and Single Protein Domain Motion via Dual Illumination Fluorescence Microscopy (2014) Nano Lett 14(10):5920-31 [PMID: 25204359; PMCID: PMC4189620]
- Spies, M.‡, Fulfilling the dream of a perfect genome editing tool (2014) PNAS 111(28):10029-30 [PMID: 24989506; PMCID: PMC4104902]
- Spies, M.‡, Two steps forward, one step back: determining XPD helicase mechanism by single-molecule fluorescence and high-resolution optical tweezers (2014) DNA Repair 20: 58-70 [PMID: 24560558; PMCID: PMC4295835]
- Honda, M, Okuno, Y, Hengel, S.R., Martín-López, J.V., Cook, C.P., Amunugama, R., Soukup, R., Subramanyam, S., Fishel, R.‡ and Spies, M‡, hMSH2-hMSH6 Recognizes Mismatches and Forms Sliding Clamps within a D-loop Recombination Intermediate (2014) PNAS 111(3):E316-325 [PMID: 24395779; PMCID: PMC3903253]
- Murfuni, I., Basile, G., Subramanyam, S., Malacaria, E., Bignami, M., Spies, M., Franchitto, A. ‡, and Pichierri, P. ‡, Survival of the replication checkpoint deficient cells requires MUS81-RAD52 function (2013) PLOS Genetics e100391 [PMID: 24204313; PMCID: PMC3814295]
- Subramanyam, S., Jones, W.T., Spies, M.‡, and Spies, M.A‡., Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction (2013) NAR 41(19):9020-9032 [PMID: 23935068; PMCID: PMC3799448]
- Qi, Z., Pugh, R.A., Spies, M., and Chemla, Y.R., Sequence-dependent base-pair stepping dynamics in XPD helicase unwinding (2013) eLife 2:e00334 [PMID: 23741615; PMCID: PMC3668415]
- Haghighat Jahromi, A., Honda, M., Zimmerman, S.C., and Spies, M. ‡, Single molecule study of the CUG repeat･MBNL1 interaction and its inhibition by small molecules (2013) NAR, 41 (13): 6687-6697. [PMID: 23661680; PMCID: PMC3711446]
- Masuda-Ozawa, T., Hoang, T., Seo, Y-S., Chen, L-F. and Spies, M.‡, Single-molecule sorting reveals how ubiquitylation affects substrate recognition and activities of FBH1 helicase. (2013) NAR, 41(6), 3576-3587. [PMID: 23393192; PMCID: PMC3616717]
- A complete list of my publications may be found at: http://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/47141158/