Wolf-Dietrich Heyer

Wolf-Dietrich Heyer

Position Title
Department Chair; Distinguished Professor; Molecular Oncology Program Co-Leader

Department of Microbiology and Molecular Genetics, College of Biological Sciences
UC Davis Comprehensive Cancer Center
Department of Molecular and Cellular Biology

3163 Life Sciences

Research Interests

Mechanism and regulation of recombinational DNA repair

Double-stranded DNA breaks (DSBs) are among the most genotoxic lesions and can be generated by ionizing radiation, drugs, or cellular processes. In eukaryotes, several pathways compete for the repair of such lesions. Homologous recombination is the critical DSB repair pathway in yeasts and an important DSB repair pathway in all eukaryotes studied. We are using  Saccharomyces cerevisiae as a lead system and employ genetical, molecular, and biochemical methods to elucidate the molecular mechanism of homologous recombination and recombinational DNA repair and its regulation by the DNA damage checkpoints. The key results are validated with human proteins and in human cells to establish lasting paradigms. Recombination has dual significance for cancer. Recombination genes are guardians of the genome and classic tumor suppressors. Hence, defects in recombination genes increase cancer risk. DNA repair and specifically recombination is also critical in anti-cancer therapy, as many modalities of treatment involve DNA damaging agents. We are applying our mechanistic insights from basic studies in more translational studies relating to cancer predisposition and anti-cancer therapy.

Grad Group Affiliations

  • Biochemistry, Molecular, Cellular and Developmental Biology
  • Integrative Genetics and Genomics
  • Microbiology
  • Pharmacology and Toxicology (PTX)
  • Integrative Pathobiology

Specialties / Focus

  • Cell Biology
  • Chromosome Biology
  • Chromosome Dynamics and Nuclear Function
  • DNA recombination
  • DNA repair


  • MIC 275 Seminar in DNA Repair and Recombination
  • GGG 295 Seminar in Molecular Genetics, Fall (biannual, even years)
  • MIC 276 Advanced Concepts DNA Metabolism, Winter (biannual, even years)
  • BCB 214 Molecular Biology, Spring


  • Our laboratory is located in LS 3243, LS 3249, LS 3144, LS 3116. My office is LS 3165. http://micro.ucdavis.edu/heyer/
    • The members of my group are: Rita Alexeeva, Dr. Shih-Shun Hung, Dr. Hang Phuong Le, Dr. Jie Liu, Dr. Diedre Reitz, Dr. João Vieira, Steven Gore, Shanaya Shah, Ash Sundaram, Kevin Yan, Mahssa Rezai, Vanessa Som, Cindy Feng, Liam Tegland, Sukhman Chathrat, Yuan Liang,

Honors and Awards

  • 1989 Richard A. Smith Award for Outstanding Scientific Achievement (Dana-Farber Cancer Institute, Harvard Medical School, USA)
  • 1995 Eduard-Adolf-Stein Award for the best Habilitation at the Philosophical-Natural Sciences Faculty of the University of Bern (CH) 1990-1995
  • 1997 Theodor-Kocher Price for the best "Young Researcher at the University of Bern 1997"
  • 2000 Chancellor's Fellow 2000-2005, University of California, Davis
  • 2002 , 2009 Outstanding Teaching Award, Biochemistry and Molecular Biology Graduate Students
  • 2010 Rothschild-Yvette Mayent-Institut Curie Award, Institut Curie, Paris (F)
  • 2011 UC Davis Chancellor's Award for Excellence in Mentoring Undergraduate Research
  • 2011 College of Biological Sciences (UC Davis) Faculty Research Award
  • 2012 Fellow, American Academy of Microbiology
  • 2016 Elected Fellow, American Association for the Advancement of Science

    Professional Societies

    • American Association for the Advancement of Science (AAAS)
    • Genetics Society of America
    • American Society of Microbiology
    • American Society for Biochemistry and Molecular Biology
    • Deutscher Hochschulverband
    • Gesellschaft fuer Biochemie und Molekularbiologie


    • 1982 Diploma Biology Free University of Berlin (Germany)
    • 1985 PhD Biology University of Bern. Switzerland
    • 1995 Habilitation Microbiology and Molecular Genetics University of Bern (Switzerland)


    Piazza, A., Rajput, P., and Heyer, W.-D. (2019) Physical and genetic assays for the study of DNA joint molecules metabolism and multi-invasion-induced rearrangements in S. cerevisiae. Methods Mol. Biol. in press.

    Tavares, E.M., Wright, W.D., Heyer, W.-D., Le Cam, E., and Dupaigne, P. (2019) Rad54 is critical for homology search and formation of synaptic complexes by the Rad51-ssDNA filament. Nature Communications 10, 4058. Jenkins, S.S., Gore, S., Guo, X., Liu, J., Ede, C.,

    Veaute, X., Jinks-Robertson, S., Kowalczykowski, S.C., and Heyer, W.-D. (2019) Role of the Srs2-Rad51 interaction domain in crossover control. Genetics 212, 1133-1145.

    Piazza, A. and Heyer, W.-D. (2019) Moving forward one step back at a time: reversibility during homologous recombination. Current Genetics May 23, doi: 10.1007/s00294-019-00995-7.

    Ehmsen, K.T., Ang, K.K.H., Wright, W.D., Davies, J.L., Younis, Y., Birman, Y., Bryant, C., Gallardo-Godoy, A., Renslo, A., Neitz, R.J., Arkin, M.R., and Heyer, W.-D. (2019) Small molecule inhibitors of a human recombination-associated ATPase, RAD54. https://www.biorxiv.org/content/10.1101/614586v1

    Meyer, D., Fu, B.X.H., Cerqueira, P.G., Chavez, M., Loeillet, S., Cerqueira, P.G., Nicolas, A., and Heyer, W.-D. (2019) Cooperation between non-essential DNA polymerases contribute to genome stability in Saccharomyces cerevisiae. DNA Repair 76, 40-49.

    Piazza, A., Shah, S., Wright, W.D., Koszul, R., and Heyer, W.-D. (2019) Dynamic processing of Displacement Loops during recombinational DNA repair. Mol. Cell 73, 1255-1266.

    [Recommended as Special Significance in Faculty of 1000 Prime https://f1000.com/prime/735034812?bd=1]

    Klein, H.L., Ang, K.K.H., Arkin, M.R., Beckwitt, E.C., Chang, Y.-H., Fan, J., Kwon, Y., Morten, M.J., Mukherjee, S., Pambos, O., el Sayyed, H., Thrall, E.S., Vieira-da-Rocha, J, Wang, Q., Wang, S., Yeh, H-Y., Biteen, Y.S., Chi, P., Heyer, W.-D., Kapanidis, A., Loparo, J.J., Strick, T.R., Sung, P., Van Houten, B., Niu, H., and Rothenberg, E. (2019) Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes. Microbial Cell 6, 65-101.

    Piazza, A. and Heyer, W.-D. (2019) Homologous recombination and the formation of complex genomic rearrangements. Trends Cell Biol. 29, 135-149.

    Wright, W.D., Shah, S.S., and Heyer, W.-D. (2018) Homologous recombination and the repair of DNA double-strand breaks. J. Biol. Chem. 293, 10524-10535.

    Piazza, A. and Heyer,W.-D. (2018) Mechanisms of multi-invasion-induced Rearrangements: Implications for physiological and pathological recombination. BioEssays 40, e1700249.

    Piazza, A., Koszul, R., and Heyer W.-D. (2018) A Proximity Ligation-based Method for Quantitative Measurement of D-loop Extension in S. cerevisiae. Meth. Enzymol. 601, 27-44.

    Piazza, A., Wright, W.D., and Heyer, W.-D. (2017) Multi-invasions are recombination intermediates that induce chromosomal rearrangements. Cell 170, 760-773.  [Highlighted in http://cancerdiscovery.aacrjournals.org/content/early/2017/08/11/2159-8290.CD-RW2017-150] [Recommended as Special Significance in Faculty of 1000 Prime http://f1000.com/prime/727879029]

    Liu, J., Wright, W., Ede, C., Wright, W.D., Gore, S.K., Jenkins, S., Freudenthal, B.D., Washington, M.T., Veaute, X, and Heyer W.-D. (2017) Srs2 helicase promotes Synthesis-Dependent Strand Annealing by disrupting DNA Polymerase Delta-extended D-loops. eLIFE 6, e22195.

    McVey, M., Khodaverdian, V.Y., Meyer, D., Cerqueira, P.G., and Heyer W.-D. (2016) Eukaryotic DNA polymerases in homologous recombination. Annu. Rev. Genet. 50, 393-421.

    Ganai, R.A., Zhang, X., Heyer, W.-D., and Johansson, E. (2016) Strand displacement synthesis by yeast DNA polymerase ε, Nucleic Acids Res. 2016 Jun 20. pii: gkw556. [Epub ahead of print].

    Spies, J., Waizenegger, A., Barton, O., Sürder, M., Wright, W.D., Heyer, W.-D., and Löbrich, M. (2016) Nek1 phosphorylates Rad54 in G2 phase to promote homologous recombination and prevent replication fork instability. Mol. Cell 62, 903-917.

    Janke, R., Kong, J., Braberg, H., Cantin, G., Yates III, J., Krogan, NJ, and Heyer, W.-D. (2016) Nonsense-mediated decay regulates key components of homologous recombination. Nucleic Acids Res. 44, 5218-5230.

    Crawley, J.N., Heyer, W.-D., and LaSalle, J.M. (2016) Autism and cancer share risk genes, pathways, and drug-targets. Trends in Genetics 32,139-146.

    Jenkins, S.S., Mukherjee, S., and Heyer, W.-D. (2016) DNA repair by homologous recombination. In: Ralph A Bradshaw and Philip D Stahl (Editors-in-Chief), Encyclopedia of Cell Biology, Vol 1, Waltham, MA: Academic Press, pp. 456-467.

    Kowalczykowski, S.C., Hunter, N., and Heyer, W.-D. (2015) DNA Recombination. Perspectives in Biology, Cold Spring Harbor Press.

    Meyer, D., Fu, B.X.H., and Heyer, W.-D. (2015) DNA Polymerases delta and lambda cooperate in repairing double-strand breaks by Microhomology Mediated End-joining in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 112, 6907-6916.

    Heyer W.-D. (2015) Regulation of Recombination and Genome Maintenance. doi:10.1101/cshperspect.a016501  In: DNA Recombination. Perspectives in Biology, Cold Spring Harbor Press. Eds. Kowalczykowski, S.C., Hunter, N., and Heyer, W.-D.

    Mason, J.M., Dusad, K., Wright, W.D., Grubb, J., Budke, B., Heyer, W.-D., Connell, P.P. Weichselbaum, R.R., and Bishop, D.K. (2015) RAD54 family translocases counter genotoxic effects of RAD51 in human tumor cells. Nucleic Acids Res. 43, 3180-3196.

    Fasching, CL., Cejka, P., Kowalczykowski, S.C., and Heyer W.-D. (2015) Top3-Rmi1 dissolve Rad51-mediated D-loops by a topoisomerase-based mechanism. Mol. Cell 57, 595-606. [Highlighted in accompanying Minireview: Haber, J.E. (2015) TOPping off Meiosis. Mol. Cell 57, 577-581.] [Highlighted in Faculty of 1000 http://f1000.com/prime/725364302?bd=1]

    Mukherjee, S., Wright, W.D., Ehmsen, K.T., and Heyer, W.-D. (2014) The Mus81-Mms4 structure-selective endonuclease undergoes nicked junction-induced conformational changes to bend its DNA substrates for cleavage. Nucleic Acids Res. 42, 6511-6522.

    Wright, W.D. and Heyer, W.-D. (2014) Rad54 is a Heteroduplex DNA Pump Modulated by Its DNA Substrates and Rad51 during D-loop Formation in Homologous Recombination. Mol. Cell 53, 420-432. [Highlighted in Faculty of 1000 http://f1000.com/prime/718262173#recommendations]

    Sneeden, J.L., Grossi, S.M., Tappin, I., Hurwitz G. and Heyer W.-D. (2013) Reconstitution of recombination-associated DNA synthesis with human proteins. Nucleic Acids Res. 41, 4913-4925.

    Zinovyev, A., Kuperstein, I., Barillot, E., and Heyer, W.-D. (2013) Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps. PLoS Computat. Biol. 9(4):e1003016.

    Zhang, X.-P., Janke, R., Kingsley, J., Luo, J., Fasching, C.L., Ehmsen, K.T., and Heyer, W.-D. (2013) A conserved sequence extending motif III of the motor domain in the Snf2-family DNA translocase Rad54 is critical for ATPase activity. PLoS ONE 8(12): e82184.

    Munoz-Galvan, S., Tous, C., Gonzalez-Blanco, M., Schwartz, E.K., Ehmsen, K.T., West, S.C., Heyer, W.-D., and Aguilera, A. (2012) Differential roles of Mus81-Mms4, Yen1, and Slx4 in the repair of replication-born double-strand breaks by sister chromatid exchange. Mol. Cell. Biol. 32, 1592-1603.

    Schwartz, E., Wright, W., Ehmsen, K.T., Evans, D., Stahlberg, H., and Heyer, W.-D. (2012) Mus81-Eme1 functions as single hetero-dimeric endonuclease. Mol. Cell. Biol. 32, 3065-3080. {Highlighted as Spotlight Article of Significant Interest Selected from This Issue by the Editors]

    Liu, J. and Heyer, W.-D. (2011) Who’s who in human recombination: BRCA2 and RAD52. Proc. Natl. Acad. Sci. USA 108, 441-442.

    Liu, J., Renault, L., Veaute, X., Fabre, F., Stahlberg, H., and Heyer, W.-D. (2011) Rad51 paralogs Rad55-Rad57 balance the anti-recombinase function of Srs2 in Rad51 filament formation. Nature 479, 245-248. [Must read in Faculty of 1000 http://f1000.com/13398957]

    Liu, J., Doty, T., Gibson, B., and Heyer, W.-D. (2010) Human BRCA2 promotes filament formation RPA-covered ssDNA. Nature Structural & Molecular Biology 17, 1260-1262. [News and Views by Zou, L. (2010) A protein giant in its entirety. Nature 467, 667-678.]

    Heyer, W.-D., Ehmsen, K.T., and Li, J. (2010) Regulation of homologous recombination in eukaryotes. Annu. Rev. Genetics. 44, 113-139.

    Li, X., Stith, C.M., Burgers, P.M., and Heyer, W.-D. (2009) PCNA is required for initiating recombination-associated DNA synthesis by DNA polymerase δ. Mol. Cell 36, 704-713.