Neil Hunter, Ph.D.
347C Briggs Hall
Meiosis is the conduit of heredity, turning diploid germ cells into haploid gametes that contain mixtures of their parental genomes. Defective meiosis is responsible for a large fraction of the ~1 million pregnancies that end in miscarriage in the U.S. each year, and causes chromosomal diseases such as Down Syndrome. Our research focuses on the chromosomal repair process known as homologous recombination, which is critical for the pairing and segregation of chromosomes during meiosis, and fuels evolution. We have developed innovative techniques to monitor the molecular steps of recombination, allowing us to dissect the molecular steps of meiotic recombination with unprecedented detail. Recent studies in mouse aim to understand how the processes of chromosome pairing and recombination are coordinated via post-translational protein modification involving ubiquitin-like molecules. These studies have led to a new paradigm for understanding meiotic crossover regulation. Current studies focus on three areas: (i) the processing of DNA strand-exchange intermediates or Joint Molecules; (ii) the regulation of meiotic prophase by an antagonistic pair of RING E3-ligase proteins, RNF212 and HEI10; (iii) oocyte quality control and the regulation of oocyte reserve.
For more information, visit the Hunter Laboratory website.
Tang, S., Wu, M.K.Y. Wu, Zhang, R. and Hunter, N. (2015). Pervasive and essential roles of the Top3-Rmi1 decatenase orchestrate recombination and facilitate chromosome segregation in meiosis. Molecular Cell 57, 607-21. PMID: 25699709
Qiao, H., Prasada, H.B.D., Yang, Y., Fong, J.H., Cloutier, J.M., Deacon, D.C., Nagel, K.E., Swartz, R.K., Strong, E., Holloway, K., Schimenti, J., Ward, J. and Hunter, N. (2014). Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination. Nature Genetics doi:10.1038/ng.2858. PMID: 24390283
Copsey, A., Tang, S. Jordan, P., Blitzblau, H., Newcombe, S., Lambacher, N. Chan, A.C., Newnham, L., Li, Z., Arumugam, P., Hochwagen, A., Neil Hunter, N., Hoffmann, E. (2013). Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions. PLoS Genetics 9, e1004071, doi:10.1371/journal.pgen.1004071. PMCID: PMC3868528
Lao, J.P.*, Cloud, V., Grubb, J., Huang, C-C., Thacker, D., Lee, C-Y., Dresser, M.E., Hunter, N.† and Bishop† (2013). Meiotic crossover control by concerted action of Dmc1-Rad51 in homolog template bias and robust homeostatic regulation. PLoS Genetics 9, e1003978, doi: 10.1371/journal.pgen.1003978. PMC3868528
Sasanuma, H., Tawaramoto, M.S., Lao, J.P., Hosaka, H., Sanda, E., Suzuki, M., Yamashita, E., Hunter, N., Shinohara, A., A. Nakagawa, A., Shinohara, A. (2013). A new protein complex promoting the assembly of Rad51 filaments. Nature Communications doi: 10.1038/ncomms2678.
Reynolds,A., Qiao, H., Yang, Y., Chen, J., Biswas, K., Holloway, K., Baudat, F., deMassy, B., Wang. J., Höög, C., Cohen, P. and Hunter, N (2013). RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis. Nature Genetics doi:10.1038/ng.2541.
Biswas, K., Das, R.,Eggington, J.M., Qiao, H., North, S.L., Stauffer, S., Burkett, S., Betty K. Martin, B.S., Southon, E, Sizemore, S.C., Pruss,D., Bowles, K.R., Roa, B.B., Hunter,N., Tessarollo, L., Wenstrup, R.J., Byrd, R.A. and Sharan, S.K. (2012). Functional evaluation of BRCA2 variants mapping to the PALB2 binding and C-terminal DNA binding domains using a mouse ES cell–based assay. Human Molecular Genetics 21,3993-4006. PMCID: PMC3428152.
QiaoH., Chen, J., Reynolds, A., Höög, C., Paddy, M. and Hunter, N. (2012). Interplay between centromeres, synaptonemal complex and homologous recombination during mammalian meiosis. PLoS Genetics 8, e1002790. PMCID: PMC3386176.
Zakheryevich,K, Tang, S., Ma, Y. and Hunter, N. (2013). Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase. Cell 149,334-47.
Hunter, N. (2011). Double duty for Exo1 during meiotic recombination. Cell Cycle 10(16), 2607-2609.
Hwang, Y-H. and Hunter, N. (2011). Mapping meiotic breaks: Spo11oligonucleotides precisely mark the spots. Genome Biology 12, 111-114. doi:10.1186/gb-2011-12-4-111.
Zakheryevich,K, Ma, Y., Tang, S., Hwang, Y-H., Boiteux, S.and Hunter, N. (2010). Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand-break resection and resolution of double-Holliday Junctions. Molecular Cell 40, 1001-1015.
Lao, J.P. and Hunter, N. (2010). Trying to avoid your sister. PLoS Biology 8(10):e1000519.
Bzymek, M., Thayer, N.H., Oh, S.D., Kleckner, N. and Hunter,N. (2010). Double-Holliday Junctions are Intermediates of DNA Break Repair. Nature 464, 937-941.
Oh S.D.,Jessop, L., Lao, J.P., Lichten, M.J. and Hunter,N.H. (2009). Stabilization and Electrophoretic Analysis of Meiotic Recombination Intermediates in Saccharomyces cerevisiae. In, Methods in Molecular Biology, Meiosis Methods and Protocols, Scott Keeney, ed. (Totowa, Humana Press).
Oh S.D., Lao, J.P. and Hunter, N. (2008). RecQ Helicase, Sgs1, and XPF-Family Endonuclease, Mus81-Mms4, Resolve Aberrant Joint Molecules During Meiotic Recombination. Molecular Cell 31, 324-336.
Hunter, N. (2008). Hop1 and the meiotic DNA-damage response. Cell 132, 731-732.
Hunter, N. (2008). The RecQ DNA helicases: Jacks-of all-trades or master-tradesmen? Cell Research 18, 328-330.
Lao, J.P, Oh, S.D., Shinohara, M., Shinohara, A. and Hunter, N. (2008). Rad52 promotes post-invasion steps of meiotic double-strand-break repair. Molecular Cell, 29, 517-524.
Shinohara, M, Oh, S.D., Hunter, N. and Shinohara, A. (2008). Crossover assurance and crossover interference are distinctly regulated by the ZMM/SIC proteins during meiosis. Nature Genetics, 40, 299-309.
Oh S.D., Lao, J.P., Hwang, P.Y-H., Taylor, A.F., Smith, G.R. and Hunter, N. (2008). Sgs1, a Bloom's helicase ortholog, prevents aberrant crossing-over by suppressing the formation of multichromatid joint molecules. Cell 130, 259-272.
Hunter, N. (2007). Meiotic Recombination. In, Molecular Genetics of Recombination, Aguilera, A. and Rothstein, R. (Eds), Topics in Current Genetics, Springer-Verlag, Heidelberg.
Cromie, G. A., Hyppa, R. W., Taylor, A. F., Zakharyevich, K., Hunter, N., and Smith, G. R. (2006). Single Holliday Junctions are intermediates of meiotic recombination. Cell 127, 1167-1178.
Martini, E., Diaz, R.L., Hunter, N. and Keeney, S. (2006). Crossover homeostasis in yeast meiosis. Cell 126, 285-295.
Hunter, N. (2004). Meiosis. In, the Encyclopedia of Biological Chemistry, Lennarz, W. and Lane, M. (Eds), Elsevier Press, San Diego. pp 610-616.
Boerner, V.G., Kleckner, N. and Hunter, N. (2004). Crossover/noncrossover differentiation, synaptonemal complex formation and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117, 29-45.
de los Santos, T., Hunter, N., Lee, C., Larkin, B., Loidl, J., and Hollingsworth, N.M. (2003). The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics, 164, 81-94.
Blat, Y., Protacio, R., Hunter, N. and Kleckner, N. (2002). Physical and functional interactions among basic chromosome organizational features govern early steps of meiotic chiasma formation. Cell, 111 791-802.
Hunter, N. and Kleckner, N. (2001). The single-end invasion: an asymmetric intermediate at the double-strand-break to double-Holliday junction transition of meiotic recombination. Cell 106, 59-70.
- HHMI Investigator Award, 2013,
- College of Biological Sciences, Faculty Research Award, 2013
- UC Davis Chancellor’s Fellow, 2009-2014
- HHMI Early Career Scientist Award, 2009-2013
- UCD Mutant Mouse Regional Resource Center Award, 2007
- France-Berkeley Fund Award,, 2006
- March of Dimes Basil O’ Connor Award (declined), 2005
- Concern Foundation Young Scholar Award, 2004-2006
- Damon Runyon Cancer Foundation Scholar Award, 2003-2006
- American Cancer Society, Institutional Research Grant, 2003
- Wellcome Trust, Prize Traveling Postdoctoral Fellowship, 1997- 2001
- Wellcome Trust, Prize Graduate Studentship, 1993-1996
- National Institutes of Health
- Howard Hughes Medical Institute
- MCB 220L BMB/CDB graduate student rotation course
- MIC 296, Advanced Concepts in DNA Metabolism
- BIS 101, Genes and Gene Expression
- MIC 191, Introduction to Research