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Department of Cell Biology and Human Anatomy

Department of Cell Biology and Human Anatomy

Neil Hunter, Ph.D.

Neil Hunter, Ph.D.

Professor
347C Briggs Hall
Davis Campus
(530) 754-4401
e-mail

Recent/Current
Research Funding

National Institutes of Health

Howard Hughes Medical Institute

Graduate Group Affiliations

Biochemistry, Molecular, Cellular and
Developmental Biology

Genetics

Microbiology

Research Interests

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.

 

Representative Publications

2015  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

2014  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

2013  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

2013  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

2013  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.

2013  Reynolds, A., Qiao, H., Yang, Y., Chen, J., Biswas, K., Holloway, K., Baudat, F., de Massy, B., Wang. J., Höög, C., Cohen, P. and Hunter, N. RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosisNature Genetics doi:10.1038/ng.2541.

2012  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. Functional evaluation of BRCA2 variants mapping to the PALB2 binding and C-terminal DNA binding domains using a mouse ES cell–based assayHuman Molecular Genetics 21, 3993-4006. PMCID: PMC3428152.

2012  Qiao H., Chen, J., Reynolds, A., Höög, C., Paddy, M. and Hunter, N. Interplay between centromeres, synaptonemal complex and homologous recombination during mammalian meiosisPLoS Genetics 8, e1002790. PMCID: PMC3386176.

2012  Zakheryevich, K, Tang, S., Ma, Y. and Hunter, N. Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvaseCell 149, 334-47.

2011  Hunter, N. Double duty for Exo1 during meiotic recombinationCell Cycle 10(16), 2607-2609.

2011  Hwang, Y-H. and Hunter, N. Mapping meiotic breaks: Spo11 oligonucleotides precisely mark the spotsGenome Biology 12, 111-114. doi:10.1186/gb-2011-12-4-111.

2010  Zakheryevich, K, Ma, Y., Tang, S., Hwang, Y-H., Boiteux, S. and Hunter, N. Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand-break resection and resolution of double-Holliday JunctionsMolecular Cell 40, 1001-1015.

2010  Lao, J.P. and Hunter, N. Trying to avoid your sisterPLoS Biology 8(10): e1000519.

2010  Bzymek, M., Thayer, N.H., Oh, S.D., Kleckner, N. and Hunter, N. Double-Holliday Junctions are Intermediates of DNA Break RepairNature 464, 937-941.

2009  Oh S.D., Jessop, L., Lao, J.P., Lichten, M.J. and Hunter, N.H. 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).

2008  Oh S.D., Lao, J.P. and Hunter, N., RecQ Helicase, Sgs1, and XPF-Family Endonuclease, Mus81-Mms4, Resolve Aberrant Joint Molecules During Meiotic Recombination. Molecular Cell 31, 324-336.

2008  Hunter, N., Hop1 and the meiotic DNA-damage response. Cell 132, 731-732.

2008  Hunter, N., The RecQ DNA helicases: Jacks-of all-trades or master-tradesmen? Cell Research 18, 328-330.

2008  Lao, J.P, Oh, S.D., Shinohara, M., Shinohara, A. and Hunter, N., Rad52 promotes post-invasion steps of meiotic double-strand-break repair. Molecular Cell, 29, 517-524.

2008  Shinohara, M, Oh, S.D., Hunter, N. and Shinohara, A., Crossover assurance and crossover interference are distinctly regulated by the ZMM/SIC proteins during meiosis. Nature Genetics, 40, 299-309.

2007  Oh S.D., Lao, J.P., Hwang, P.Y-H., Taylor, A.F., Smith, G.R. and Hunter, N., Sgs1, a Bloom's helicase ortholog, prevents aberrant crossing-over by suppressing the formation of multichromatid joint molecules. Cell 130, 259-272.

2006  Hunter, N., Meiotic Recombination. In, Molecular Genetics of Recombination, Aguilera, A. and Rothstein, R. (Eds), Topics in Current Genetics, Springer-Verlag, Heidelberg.

2006  Cromie, G. A., Hyppa, R. W., Taylor, A. F., Zakharyevich, K., Hunter, N., and Smith, G. R., Single Holliday Junctions are intermediates of meiotic recombination. Cell 127, 1167-1178.

2006  Martini, E., Diaz, R.L., Hunter, N. and Keeney, S., Crossover homeostasis in yeast meiosis. Cell 126, 285-295.

2004  Hunter, N., Meiosis. In, the Encyclopedia of Biological Chemistry, Lennarz, W. and Lane, M. (Eds), Elsevier Press, San Diego. pp 610-616.

2004  Boerner, V.G., Kleckner, N. and Hunter, N., Crossover/noncrossover differentiation, synaptonemal complex formation and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117, 29-45.

2003  de los Santos, T., Hunter, N., Lee, C., Larkin, B., Loidl, J., and Hollingsworth, N.M., 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.

2002  Blat, Y., Protacio, R., Hunter, N. and Kleckner, N., Physical and functional interactions among basic chromosome organizational features govern early steps of meiotic chiasma formation. Cell, 111 791-802.

2001  Hunter, N. and Kleckner, N., The single-end invasion: an asymmetric intermediate at the double-strand-break to double-Holliday junction transition of meiotic recombination. Cell 106, 59-70.

 

Recent/Current Teaching

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

 

Honors and Awards

  • 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