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Department of Biochemistry

Research Interests

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.

Recent Publications

• Pugh, R. A., Wu, C. G., and Spies, M., Regulation of translocation polarity by helicase domain 1 in SF2B helicases.(2012) EMBO J 31: 503 - 514 pdf
  
  Honda, M., Okuno, Y., Yoo, J., Ha, T., and Spies, M., Tyrosine phosphorylation enhances RAD52-mediated annealing by modulating its DNA binding(2011) EMBO Journal 30:3368-82 pdf

  Grimme, J.M. and Spies, M. FRET-based assay to monitor DNA binding and annealing by Rad52 recombination mediator protein (2011) Methods in Molecular Biology, 745:463-83
  
  Grimme JM, Honda M, Wright R, Okuno Y, Rothenberg E, Mazin AV, Ha T and Spies, M., Human Rad52 binds and wraps single-stranded DNA and mediates annealing via two hRad52-ssDNA complexes. (2010) NAR, 38(9):2917-30 pdf
  
  Spies, M. and Ha, T., "Inching over hurdles: how DNA helicases move on crowded lattices?": (2010) Cell Cycle, 9 (9): 1742-9 pdf
  
  Pugh, R. A., Honda, M., and Spies, M. Ensemble and single-molecule fluorescence-based assays to monitor DNA binding, translocation and unwinding by FeS-containing helicases (2010) Methods, 51(3):313-21pdf

  Honda, M., Park, J., Pugh R.A., Ha, T. and Spies, M., Single-molecule analysis reveals differential effect of ssDNA-binding proteins on DNA translocation by XPD helicase. (2009) Mol.Cell35 (5), 694-703 pdf
  
  Rothenberg, E., Grimme, J. M., Spies, M. and Ha, T., Rad52 protein mediates directionally biased homology search and DNA annealing through continuous association of two Rad52-ssDNA complexes. (2008) PNAS105 (51) 20274-20279 pdf

  Pugh, R. A., Lin, Y., Eller C., Leesley H., Cann, I. K.O., and Spies, M. Ferroplasma acidarmanus RPA2 facilitates efficient unwinding of forked DNA substrates by monomers of XPD helicase.(2008) JMB383(5): 982-98 pdf
  
  Lin, Y., Lin, L.-J., Sriratana, P., Coleman, K., Ha, T., Spies, M., Cann, I.K.O. Engineering of functional replication protein A homologs based on insights in evolution 1 of 2 oligonucleotide/oligosaccharide binding (OB) folds. (2008); J. Bac, 190 (17) 5766-5780 pdf

  Pugh, R. A., Honda, M., Leesley, H., Thomas, A., Lin, Y., Nilges, M. J., Cann, I. K., and Spies, M.. 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.(2008) J Biol Chem, 283: 1732-1743 pdf

  
  
  
• Visit Google Scholar for all of Dr. Maria Spies's publications.