Rodney

Rothstein

Rodney Rothstein is pictured.
Professor
701 W. 168 St., HHSC 1608
New York
NY
10032
Office Phone: 
(212) 305-1733
Lab Phone: 
(212) 305-1734
Fax: 
(212) 923-2090
Short Research Description: 

Yeast genetics; mechanisms of genetic recombination; control of genome stability; functional genomics.

Full Research Description: 

By using budding yeast as an experimental organism, we are able to study essential biological processes such as the mechanisms underlying the recognition and repair of DNA damage. The role that genetic recombination plays during repair is an integral part of our research.

We are exploring the biological response to DNA damage by studying a central recombination protein, Rad52, a ribonuclease reductase inhibitor that responds degrades after DNA damage, Sml1, and a topoisomerase helicase complex necessary for resistance to DNA damaging agents, Top3/Sgs1.

The availability of a complete gene disruption library is another tool that aids our research. By developing methods to enhance the utility of this resource, we are facilitating genome-wide analysis of not only budding yeast, but other species as well.

Representative Publications: 
  • Miné-Hattab, J. and Rothstein, R. Increased chromosome mobility facilitates homology search during recombination. Nature Cell Biol., 14: 510–517, 2012.
  • Thorpe, P.H., Dittmar, J.C. and Rothstein, R. ScreenTroll: A searchable database to compare genome-wide yeast screens. Database, doi:10.1093/database/bas022, 2012.
  • García-Rodríguez, N., del Carmen Díaz de la Loza, M., Andreson, B., Monje-Casas, F., Rothstein, R. and Wellinger, R.E. Impaired Manganese Metabolism Causes Mitotic Misregulation. J. Biol. Chem., doi: 10.1074/jbc.M112.358309, 2012.
  • Bernstein, K.A., Reid, R.J.D., Sunjevaric, I., Demuth, K., Burgess, R.C. and Rothstein, R. The Shu complex, which contains Rad51 paralogues, promotes DNA repair through inhibition of the Srs2 anti-recombinase. Molec. Biol. Cell 22: 1599-1607, 2011.
  • León Ortiz AM, Reid RJ, Dittmar JC, Rothstein R, Nicolas A. Srs2 overexpression reveals a helicase-independent role at replication forks that requires diverse cell functions. DNA Repair (Amst). 10: 506-17, 2011.
  • Eckert-Boulet, N., Rothstein, R. and Lisby, M. Cell biology of homologous recombination in yeast.Methods Mol Biol. 745: 523-36, 2011.
  • Thorpe, P.H., Alvaro, D.A., Lisby, M. and Rothstein, R. Bringing Rad52 foci into focus. J. Cell Biol. 194: 665-667, 2011.
  • Reid RJ, González-Barrera S, Sunjevaric I, Alvaro D, Ciccone S, Wagner M, Rothstein R. Selective ploidy ablation, a high-throughput plasmid transfer protocol, identifies new genes affecting topoisomerase I-induced DNA damage. Genome Res., 3:477-86, 2011.
  • Chang M, Dittmar JC, Rothstein R. Long telomeres are preferentially extended during recombination-mediated telomere maintenance. Nat Struct Mol Biol., 4:451-456, 2011.
  • Bernstein KA, Gangloff S, Rothstein R. The RecQ DNA helicases in DNA repair. Annu Rev Genet., 44:393-417, 2010.
  • Dittmar JC, Reid RJ, Rothstein R. ScreenMill: a freely available software suite for growth measurement, analysis and visualization of high-throughput screen data. BMC Bioinformatics, 11:353, 2010.
  • Andreson BL, Gupta A, Georgieva BP, Rothstein R. The ribonucleotide reductase inhibitor, Sml1, is sequentially phosphorylated, ubiquitylated and degraded in response to DNA damage. Nucleic Acids Res. 38(19):6490-501. 2010.
  • Barlow, J.H. and Rothstein, R. Timing is everything: cell cycle control of Rad52. Cell Division, 5: 7, 2010.
  • Mortensen, U.H., Lisby, M. and Rothstein, R. Rad52. Current Biol, 19(16): R676-7, 2009.
  • Chang, M., Luke, B., Kraft, C., Li, Z., Peter, M., Lingner, J. and Rothstein, R. Telomerase is essential to alleviate pif1-induced replication stress at telomeres. Genetics, 183(3): 779-91, 2009.
  • Burgess, R.C., Lisby, M., Altmannova, V., Krejci, L., Sung, P. and Rothstein, R. Localization of recombination proteins and Srs2 reveals anti-recombinase function in vivo. J Cell Biol, 185(6): 969-81, 2009.
  • Lisby, M. and Rothstein, R. Choreography of recombination proteins during the DNA damage response. DNA Repair, 8(9): 1068-76, 2009.
  • Bernstein, K.A. and Rothstein, R. At loose ends: resecting a double-strand break. Cell, 137(5): 807-10, 2009.
  • Thorpe, P.H., Bruno, J. and Rothstein, R. Kinetochore asymmetry defines a single yeast lineage. PNAS, 106(16): 6673-8, 2009.
  • Barlow, J.H. and Rothstein, R. Rad52 recruitment is DNA replication independent and regulated by Cdc28 and the Mec1 kinase. EMBO J, 28: 1121-30, 2009.
  • Bernstein, K.A., Shor, E., Sunjevaric, I., Fumasoni, M., Burgess, R.C., Foiani, M., Branzei, D. and Rothstein, R.Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair. EMBO J, 28: 915-25, 2009.
  • Thorpe, P.H., Bruno, J. and Rothstein, R. Modeling stem cell asymmetry in yeast. Cold Spring Harb Symp Quant Biol, 73: 81-8, 2008.
  • Reid, R.J., Sunjevaric, I., Voth, W.P., Ciccone, S., Du, W., Olsen, A.E., Stillman, D.J. and Rothstein, R.Chromosome-scale genetic mapping using a set of 16 conditionally stable Saccharomyces cerevisiae chromosomes. Genetics, 180: 1799-808, 2008.
  • Weinstein, J. and Rothstein, R. The genetic consequences of ablating helicase activity and the Top3 interaction domain of Sgs1. DNA Repair, 7(4): 558-71, 2008.
  • Barlow, J.H., Lisby, M. and Rothstein, R. Differential regulation of the cellular response to DNA double-strand breaks in G1. Molecular Cell, 30(1): 73-85, 2008.
  • Plate, I., Albertsen, L., Lisby, M., Hallwyl, S.C.L., Feng, Q., Seong, C., Rothstein, R., Sung, P. and Mortensen, U.H.Rad52 multimerization is important for its nuclear localization in Saccharomyces cerevisiae.DNA Repair 7: 57-66, 2008.
  • Kanaar, R. Wyman, C. and Rothstein, R. Quality control in DNA break metabolism: in the 'end', it's a good thing. EMBO J 27: 581-588, 2008.
  • Aguilera, A. and Rothstein, R. In: Topics in Current Genetics - Molecular Genetics of Recombination, Springer-Verlag, Berlin, 2007
  • Alvaro D., Lisby M. and Rothstein R. Genome-Wide Analysis of Rad52 Foci Reveals Diverse Mechanisms Impacting Recombination. PLoS Genet 3(12): e228, 2007.
  • Torres-Rosell, J., Sunjevaric, I., De Piccoli, G., Sacher, M., Eckert-Boulet, N., Reid, R., Jentsch, S., Rothstein, R., Aragón, L., Lisby, M. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol. 9 (8): 923-31, 2007
  • Burgess, R.C., Rahman, S., Lisby, M., Rothstein, R. and Zhao, X. The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination. Mol Cell Biol. 27 (17): 6153-62, 2007
  • Thorpe, P.H., González-Barrera, S. and Rothstein, R. More is not always better: the genetic constraints of polyploidy. Trends in Genetics, 23(6): 263-266, 2007
  • Lisby, M. and Rothstein, R. The cell biology of mitotic recombination in Saccharomyces cerevisiae.In: Topics in Current Genetics - Molecular Genetics of Recombination (A. Aguilera and R. Rothstein, eds.), Springer-Verlag, Berlin, pp. 317-333, 2007
  • Feng, Q., Düring L., Antúnez de Mayolo, A., Lettier G., Lisby M., Erdeniz N., Mortensen H.U., Rothstein, R.Rad52 and Rad59 exhibit both overlapping and distinct functions. DNA Repair, 6(1): 27-37, 2007
  • Lettier G., Feng, Q., Antúnez de Mayolo, A., Erdeniz, N., Reid, R.J.D., Lisby, M., Mortensen, H.M. and Rothstein, R. The role of DNA double-strand breaks in spontaneous homologous recombination in S. cerevisiae. PLoS Genet, 2(11): e194, 2006.
  • Alvaro D., Sunjevaric I., Reid R., Lisby M., and Rothstein R. Systematic Hybrid LOH: a new method to reduce false positives and negatives during screening of yeast gene deletion libraries. Yeast, 23: 1097-1106, 2006
  • Wagner, M., Price, G. and Rothstein, R. The absence of Top3 reveals an interaction between the Sgs1 and Pif1 DNA helicases in Saccharomyces cerevisiae. Genetics, 174: 555-73, 2006.
  • Antúnez de Mayolo, A., Lisby, M., Erdeniz, N., Thybo, T., Mortensen, U.H., and Rothstein, R. Multiple start codons and phosphorylation result in discrete Rad52 protein species. Nucleic Acids Res, 34: 2587-97, 2006.
  • Thorpe, P.H., Marrero, V.A., Savitsky, M.H., Sunjevaric, I., Freeman, T.C., Rothstein, R. Cells expressing murine RAD52 splice variants favor sister chromatid repair. Molec. Cell. Biol, 26: 3752-63, 2006.
  • Shor, E., Weinstein, J. and Rothstein, R A genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: Four genes involved in error-free DNA repair. Genetics 169: 1275-1289, 2005.
  • Lisby, M. and Rothstein, R. DNA repair: keeping it together. Current Biol. 14: R994-R996, 2004.
  • Lisby, M., Barlow, J.H., Burgess, R.C. and Rothstein, R. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 118: 699-713, 2004.
  • Reid, R.J.D and Rothstein, R. Stay close to your sister. Molecular Cell 14: 418-420,2004.
  • Lisby, M. and Rothstein, R. DNA damage checkpoint and repair centers. Current Opinion in Cell Biology 16:328-334, 2004.
  • Lisby, M., Antúnez de Mayolo, A., Mortensen, U.H., and Rothstein, R. Cell Cycle regulated centers of DNA double-strand break repair. Cell Cycle, 2: 479-483, 2003.
  • Lisby, M., Mortensen, U.H. and Rothstein, R. Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre. Nature Cell Biol. 5: 572-577, 2003.
  • Chabes, A., Georgieva, B., Domkin, V., Zhao, X., Rothstein, R. and Thelander, L. Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase. Cell, 112: 391-401, 2003.
  • Shor, E., Gangloff, S., Wagner, M., Weinstein, J., Price, G., and Rothstein, R. Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae. Genetics, 162:647-662, 2002.
  • Mortensen, U.H., Erdeniz, N., Feng, Q. and Rothstein, R. A molecular genetic dissection of the evolutionarily conserved N-terminus of yeast Rad52. Genetics, 161: 549-562, 2002.
  • Zhao, X. and Rothstein, R. The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage.Proc. Natl. Acad. Sci. USA 99: 3746-3751, 2002.
  • Reid, R.J.D., Sunjevaric, I.Keddache, M. and Rothstein, R. Efficient PCR-based gene disruption inSaccharomyces strains using intergenic primers. Yeast 19: 319-328, 2002.
  • Lisby, M., Rothstein, R. and Mortensen, U.H. Rad52 forms DNA repair and recombination centers during S phase. Proc. Natl. Acad. Sci. USA 98: 8276-8282, 2001.
  • Zhao, X., Muller, E.G.D. and Rothstein, R. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Molecular Cell 2: 329-340, 1998.
  • Zou, H. and Rothstein, R. Holliday junctions accumulate in replication mutants via a RecA homolog-independent mechanism. Cell 90: 87-96, 1997
  • Mortensen, U.H., Bendixen, C., Sunjevaric, I. and Rothstein, R. DNA strand annealing is promoted by the yeast Rad52 protein. Proc. Natl. Acad. Sci. USA 93: 10729-10734, 1996.

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