Maria Spies, PhD

Portrait
Associate Professor of Biochemistry
Associate Professor of Radiation Oncology

Contact Information

Office: 4-532 Bowen Science Building
Iowa City, IA 52242
319-335-3221

Education

BS, Physics/Biophysics, Peter the Great St. Petersburg Polytechnic University
MS, Physics/Biophysics, Peter the Great St. Petersburg Polytechnic University
PhD, Biological Sciences/Structural Biology, Graduate School of Science, Osaka University

Fellow, Dept. of Microbiology, University of California at Davis

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Research Summary

Work in my lab focuses on genome caretakers at the intersection of the 3Rs of DNA maintenance, Replication, Recombination and DNA Repair. Understanding the molecular bases and regulation of these processes is fundamentally important because accumulation or incomplete repair of DNA lesions can lead to genetic instability and chromosomal rearrangements causing cancer and cell senescence, while erroneous attempts to reestablish stalled or collapsed replication forks may result in diseases associated with progressive expansion of repeated sequences (such as myotonic dystrophy and Fragile X, syndrome among many others). We study DNA repair at the most fundamental level by first deconstructing the macromolecular ensembles orchestrating distinct DNA repair events down to the level of individual proteins. By combining physical and single-molecule biochemistry, we then investigate molecular mechanisms of the key players in these DNA repair pathways and how other protein partners and posttranslational modifications affect their action. We are also developing novel experimental approaches allowing us to sort and interrogate individual macromolecular complexes extracted from human cells and tissue samples. The resulting integrated in vivo – in vitro – in singulo approach is aimed at identifying features of genome caretaker proteins that can be exploited in designing the new therapeutics. Current projects in our lab focus on regulation of RAD51 protein, which orchestrates the central step of homologous genetic recombination, on deciphering the molecular mechanisms and regulation of several motor proteins (FBH1, FANCJ, RTEL, CHLR1 and XPD) involved in control of RAD51-mediated recombination, replication fork progression and chromosome segregation, as well as on interplay between recombination and mismatch repair.

Publications

Hengel, S., Spies, M. & Spies, M. (In Press). Small Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy. Cell Chemical Biology.

Spies, M., Smith, B. (2017). Protein-Nucleic Acids Interactions: New Ways of Connecting Structure, Dynamics and Function. (Vols. 9). (4), pp. 289-291. Biophys. Rev.. PMID: 28776257.

Spies, M., Malkova, A. (Eds.) (In Press). Mechanisms of Homologous Recombination and Genome Rearrangements - Part 1. Elsevier, Academic Press.

Subramanyam, S., Spies, M. (In Press). Expression, purification and biochemical evaluation of human RAD51 protein. Methods in Enzymology.

Spies, M., Chemla, Y. (Eds.) (2017). Single-molecule enzymology: Nanomechanical Manipulation and Hybrid Methods. Methods in Enzymology, Academic Press, Elsevier.

Spies, M. (2017). A Time for Promiscuity in a Eukaryotic Recombinase. (Vols. 292). (26), pp. 11136-11137. JBC. PMID: 27793278.

Spies, M., Malkova, A. (Eds.) (In Press). Mechanisms of Homologous Recombination and Genome Rearrangements - Part 2. Elsevier, Academic Press.

Spies, M., Chemla, Y. R. (2016). Single-molecule enzymology: fluorescence-based and high-throughput methods. In Methods in enzymology. pp. 581. Elsevier.

Chen, R., Subramanyam, S., Elcock, A. H., Spies, M. & Wold, M. S. (2016). Dynamic binding of replication protein a is required for DNA repair. (Vols. 44). (12), pp. 5758-72. Nucleic acids research. PMID: 27131385.

Bain, F. E., Wu, C. G. & Spies, M. (2016). Single-molecule sorting of DNA helicases. (Vols. 108). pp. 14-23. Methods (San Diego, Calif.). PMID: 27223403.

Spies, M. (Eds.) (2016). Single-molecule enzymology: Fluorescene-Based and High-Throughput Methods. Methods in Enzymology, Elsevier, Academic Press.

Subramanyam, S., Ismail, M., Bhattacharya, I. & Spies, M. (2016). Tyrosine phosphorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamics. Proceedings of the National Academy of Sciences of the United States of America. PMID: 27671650.

Boehm, E. M., Subramanyam, S., Ghoneim, M., Washington, M. T. & Spies, M. (2016). Quantifying the Assembly of Multicomponent Molecular Machines by Single-Molecule Total Internal Reflection Fluorescence Microscopy. pp. 105-145. Methods in enzymology. PMID: 27793278.

Wu, C. G., Spies, M. (2016). G-quadruplex recognition and remodeling by the FANCJ helicase. Nucleic acids research. PMID: 27342280.

Boehm, E. M., Spies, M. & Washington, M. T. (2016). PCNA tool belts and polymerase bridges form during translesion synthesis. Nucleic acids research. PMID: 27325737.

Boehm, E. M., Powers, K. T., Kondratick, C. M., Spies, M., Houtman, J. C. & Washington, M. T. (2016). The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase ? Mediates Its Interaction with the C-terminal Domain of Rev1. (Vols. 291). (16), pp. 8735-44. The Journal of biological chemistry. PMID: 26903512.

Hengel, S. R., Malacaria, E., da Folly Silva Constantino, L., Bain, F. E., Diaz, A., Koch, B. G., Yu, L., Wu, M., Pichierri, P., Spies, M. A. & Spies, M. (2016). Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells. (Vols. 5). eLife. PMID: 27434671.

Spies, M., Fishel, R. (2015). Mismatch repair during homologous and homeologous recombination. (3), pp. a022657. Cold Spring Harbor perspectives in biology. PMID: 25731766.

Spies, M. (2014). Fulfilling the dream of a perfect genome editing tool. (Vols. 11). (28), pp. 10029-30. Proc Natl Acad Sci U S A. PMID: 24989506.

Spies, M. (2014). Two steps forward, one step back: determining XPD helicase mechanism by single-molecule fluorescence and high-resolution optical tweezers. DNA Repair (Amst), 20, 58-70. PMID: 24560558.

Ghoneim, M., Spies, M. (2014). Direct correlation of DNA binding and single protein domain motion via dual illumination fluorescence microscopy. (Vols. 14). (10), pp. 5920-31. Nano Lett. PMID: 25204359.

Honda, M., Okuno, Y., Hengel, S. R., Martin-Lopez, J. V., Cook, C. P., Amunugama, R., Soukup, R. J., Subramanyam, S., Fishel, R. & Spies, M. (2014). hMSH2-hMSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate. (Vols. 11). (3), pp. E316-25. Proc Natl Acad Sci USA. PMID: 24395779.

Masuda-Ozawa, T., Hoang, T., Seo, Y. S., Chen, L. F. & Spies, M. (2013). Single-molecule sorting reveals how ubiquitylation affects substrate recognition and activities of FBH1 helicase. (Vols. 41). (6), pp. 3579-3587. NAR. PMID: 23393192.

Beyer, D. C., Ghoneim, M. K. & Spies, M. (2013). Structure and Mechanisms of SF2 DNA Helicases. In , M. Spies (Eds.) DNA Helicases. pp. 47-73. Advances in experimental medicine and biology. PMID: 23161006.

Qi, Z., Pugh, R. A., Spies, M. & Chemla, Y. R. (2013). Sequence-dependent base pair stepping dynamics in XPD helicase unwinding. (Vols. 2). pp. e00334. eLife. PMID: 23741615.

Spies, M. (2013). There and back again: new single-molecule insights in the motion of DNA repair proteins. Current opinion in structural biology, 23(1), 154-60. PMID: 23260129.

Wu, C. G., Spies, M. (2013). Overview: what are helicases?. In , M. Spies (Eds.) DNA Helicases. pp. 16-Jan. Advances in experimental medicine and biology. PMID: 23161004.

Haghighat Jahromi, A., Honda, M., Zimmerman, S. C. & Spies, M. (2013). Single-molecule study of the CUG repeat-MBNL1 interaction and its inhibition by small molecules. Nucleic acids research. PMID: 23661680.

Subramanyam, S., Jones, W. T., Spies, M. & Spies, M. A. (2013). Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction. NAR. PMID: 23935068.

Spies, M. (2013). DNA repair: trust but verify. (23), pp. R115-7. Curr Biol. PMID: 23391386.

Murfuni, I., Basile, G., Subramanyam, S., Malacaria, E., Bignami, M., Spies, M., Franchitto, A. & Pichierri, P. (2013). Survival of the replication checkpoint deficient cells requires MUS81-RAD52 function. PLOS Genetics. PMID: 24204313.

Spies, M. (Eds.) (2013). DNA Helicases and DNA Motor Proteins. (ISSN 0065-2598) Springer.

Pugh, R. A., Wu, C. G. & Spies, M. (2012). Regulation of translocation polarity by helicase domain 1 in SF2B helicases. (Vols. 31). (2), pp. 503-14. The EMBO journal. PMID: 22081110.

Grimme, J. M., Spies, M. (2011). FRET-based assays to monitor DNA binding and annealing by Rad52 recombination mediator protein. (Vols. 745). pp. 463-83. Methods in molecular biology (Clifton, N.J.). PMID: 21660711.

Honda, M., Okuno, Y., Yoo, J., Ha, T. & Spies, M. (2011). Tyrosine phosphorylation enhances RAD52-mediated annealing by modulating its DNA binding. (Vols. 30). (16), pp. 3368-82. The EMBO journal. PMID: 21804533.

Grimme, J. M., Honda, M., Wright, R., Okuno, Y., Rothenberg, E., Mazin, A. V., Ha, T. & Spies, M. (2010). Human Rad52 binds and wraps single-stranded DNA and mediates annealing via two hRad52-ssDNA complexes. (Vols. 38). (9), pp. 2917-30. Nucleic acids research. PMID: 20081207.

Spies, M., Ha, T. (2010). Inching over hurdles: how DNA helicases move on crowded lattices. (Vols. 9). (9), pp. 1742-9. Cell cycle (Georgetown, Tex.). PMID: 20436294.

Pugh, R. A., Honda, M. & Spies, M. (2010). Ensemble and single-molecule fluorescence-based assays to monitor DNA binding, translocation, and unwinding by iron-sulfur cluster containing helicases. (Vols. 51). (3), pp. 313-21. Methods (San Diego, Calif.). PMID: 20167274.

Honda, M., Park, J., Pugh, R. A., Ha, T. & Spies, M. (2009). Single-molecule analysis reveals differential effect of ssDNA-binding proteins on DNA translocation by XPD helicase. (Vols. 35). (5), pp. 694-703. Molecular Cell. PMID: 19748362.

Rothenberg, E., Grimme, J. M., Spies, M. & Ha, T. (2008). Rad52 protein mediates directionally biased homology search and DNA annealing through continuous association of two Rad52-ssDNA complexes. (Vols. 105). (51), pp. 20274-9. Proceedings of the National Academy of Sciences of the United States of America. PMID: 19074292.

Pugh, R. A., Honda, M., Leesley, H., Thomas, A., Lin, Y., Nilges, M. J., Cann, I. K. & Spies, M. (2008). The iron-containing domain is essential in Rad3 helicases for coupling of ATP hydrolysis to DNA translocation and for targeting the helicase to the single-stranded DNA-double-stranded DNA junction. (Vols. 283). (3), pp. 1732-43. The Journal of Biological Chemistry. PMID: 18029358.

Pugh, R. A., Spies, M. (2008). DNA Helicases, Chemistry and Mechanisms of. Wiley Encyclopedia of Chemical Biology.

Lin, Y., Lin, L. J., Sriratana, P., Coleman, K., Ha, T., Spies, M. & Cann, I. K. (2008). Engineering of functional replication protein a homologs based on insights into the evolution of oligonucleotide/oligosaccharide-binding folds. (Vols. 190). (17), pp. 5766-80. Journal of Bacteriology. PMID: 18586938.

Pugh, R. A., Lin, Y., Eller, C., Leesley, H., Cann, I. K. & Spies, M. (2008). Ferroplasma acidarmanus RPA2 facilitates efficient unwinding of forked DNA substrates by monomers of FacXPD helicase. (Vols. 383). (5), pp. 982-98. Journal of Molecular Biology. PMID: 18801373.

Grimme, J. M., Spies, M. (2007). DNA helicases in homologous recombination. Molecular Genetics, Biophysics and Medicine Today, Bresler Memorial Lectures II, 123-140.

Spies, M., Amitani, I., Baskin, R. J. & Kowalczykowski, S. C. (2007). Translocation by single-molecules of a RecBCD motor mutant reveals a switch in motor subunit usage at X. pp. 694-705, highlight 651-653. Cell.

Spies, M., Kowalczykowski, S. C. (2006). The RecA binding locus of RecBCD is a general domain for recruitment of DNA strand exchange proteins. (Vols. 21). (4), pp. 573-80. Molecular Cell. PMID: 16483938.

Spies, M., Dillingham, M. S. & Kowalczykowski, S. C. (2005). Translocation by the RecB motor is an absolute requirement for {chi}-recognition and RecA protein loading by RecBCD enzyme. (Vols. 280). (44), pp. 37078-87. The Journal of Biological Chemistry. PMID: 16041060.

Spies, M., Dillingham, M. S. & Kowalczykowski, S. C. (2005). DNA helicases. McGraw-Hill Professional (Eds.) McGraw-Hill Encyclopedia of Science & Technology.

Spies, M., Kowalczykowski, S. C. (2004). Homologous recombination by RecBCD and RecF Pathways., ASM Press Washington D.C. (Eds.) pp. 389-403. The Bacterial Chromosome.

Spies, M., Bianco, P. R., Dillingham, M. S., Handa, N., Baskin, R. J. & Kowalczykowski, S. C. (2003). A molecular throttle: the recombination hotspot chi controls DNA translocation by the RecBCD helicase. (Vols. 114). (5), pp. 647-54. Cell. PMID: 13678587.

Dillingham, M. S., Spies, M. & Kowalczykowski, S. C. (2003). RecBCD enzyme is a bipolar DNA helicase. (Vols. 423). (6942), pp. 893-7. Nature. PMID: 12815438.

Spies, M., Dillingham, M. S. & Kowalczykowski, S. C. (2003). DNA helicases. McGraw-Hill Professional (Eds.) pp. 95-98. McGraw-Hill 2003 Yearbook of Science & Technology.

Spies, M., Kil, Y., Masui, R., Kato, R., Kujo, C., Ohshima, T., Kuramitsu, S. & Lanzov, V. (2000). The RadA protein from a hyperthermophilic archaeon Pyrobaculum islandicum is a DNA-dependent ATPase that exhibits two disparate catalytic modes, with a transition temperature at 75 degrees C. (Vols. 267). (4), pp. 1125-37. European journal of biochemistry / FEBS. PMID: 10672022.

Mirlina, E. D., Manicheva, O. A., Visnevsky, B. I., Silbergleit Arc, S., Tchernayenko, V. M. & Lanzov, V. A. (1996). PCR-based molecular diagnostics procedure for revealing Mycobacterium tuberculosis complex: visualization of the results using avidinbiotin system. (Vols. 2). pp. 48-55. Biotehnologia (Biotechnology Russ.).

Koudrova, M., Arnold, H. H., Koster, M. & Braun, T. (1996). Regulation and function of SF/HGF during migration of limb muscle precursor cells in chicken. (Vols. 180). (2), pp. 566-578. Developmental Biology.