Eric Alani
Professor of Genetics

Phone

607-254-4811

Address

Department of Molecular Biology & Genetics
459 Biotechnology Building
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Background

Eric Alani is a Professor of Genetics in the Department of Molecular Biology and Genetics. He received a B.S. degree from Massachusetts Institute of Technology in 1984 and a Ph.D. from Harvard University in 1990. He was a Life Sciences Research Foundation Merck fellow (1991-1994) at Harvard Medical School in Boston before joining the faculty at Cornell in 1995. Dr. Alani is currently a member of the Genetics Society of America and the American Society for Microbiology. Dr. Alani's research has been supported by the National Institutes of Health and the United States Department of Agriculture.

Research Description

Highly conserved mismatch repair (MMR) systems have been identified in organisms ranging from bacteria to humans that recognize and repair base pair and small insertion/deletion mismatches that arise as the result of DNA replication errors, DNA damage, and genetic recombination.  These systems are thought to improve the fidelity of DNA replication by about three orders of magnitude.  In humans, mutations in MMR genes have been correlated to both an increased mutation rate and a predisposition to a hereditary form of colorectal cancer (HNPCC).  The goal of our laboratory is to understand how MMR proteins interact to prevent replication errors and to modulate genetic recombination. We are addressing these questions in the model organism baker's yeast (Saccharomyces cerevisiae) using a combination of genetic and biochemical approaches. more

Selected Publications

Click here for Dr. Alani's PubMed listing.

Evans, E., Sugawara, N., Haber, J. E., and Alani, E. (2000). The Saccharomyces cerevisiae Msh2 mismatch repair protein localizes to recombination intermediates in vivo. Mol. Cell 5, 789-799.

Argueso, J. L., Kijas, A. W., Sarin, S., Heck, J., Waase, M., and Alani, E. (2003). Systematic mutagenesis of the Saccharomyces cerevisiae MLH1 gene reveals distinct roles for Mlh1p in meiotic crossing over and in vegetative and meiotic mismatch repair. Mol. Cell. Biol. 23, 873-886..

Alani, E., Lee, J. Y., Schofield, M. J., Kijas, A. W., Hsieh, P. and Yang, W. (2003) Crystal structure and biochemical analysis of the MutS-ADP· BeFx complex suggests a conserved mechanism for ATP interactions in mismatch repair. J. Biol. Chem. 278, 16088-16094.

Kijas, A. W., Studamire, B., and Alani, E. (2003) msh2 separation of function mutations confer defects in the initiation steps of mismatch repair. J. Mol. Biol. 331,123-138.

Sugawara, N., Goldfarb, T., Studamire, B., Alani, E., and Haber, J. E. (2004) Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and msh6 but not Pms1. Proc. Natl. Acad. Sci. USA 101, 9315-9320.

Argueso, J. L., Wanat, J., Gemici, Z., and Alani, E. (2004). Competing crossover pathways act during meiosis in Saccharomyces cerevisiae. Genetics, 168, 1805-1816.

Goldfarb, T., and Alani, E. (2005). Distinct roles for the Saccharomyces cerevisiae mismatch repair proteins in heteroduplex rejection, mismatch repair, and non-homologous tail removal. Genetics 169, 563-574.

Jiang, J., Bai, L., Surtees, J. A., Gemici, Z., Wang, M. D., and Alani, E. (2005). Detection of high affinity mismatch binding and sliding clamp modes for the MSH2-MSH6 mismatch recognition complex by single-molecule unzipping force analysis. Mol. Cell 20, 771-781.

Lee, S. D., and Alani, E. (2006). Analysis of interactions between mismatch repair initiation factors and the replication processivity factor PCNA. J. Mol. Biol. 355, 175-184.

Heck, J. A., Argueso, J. L., Gemici, Z., Reeves, G. R., Bernard, A., Aquadro, C. F., and Alani, E. (2006). Negative epistasis between natural variants of the Saccharomyces cerevisiae MLH1 and PMS1 genes results in a defect in mismatch repair. Proc. Natl. Acad. Sci. USA 103, 3256-3261.

Surtees J. A., and Alani, E. (2006). Mismatch Repair Factor MSH2-MSH3 binds and alters the conformation of branched DNA structures predicted to form during genetic recombination. J. Mol. Biol. 360, 523-536.

Heck, J. A., Gresham, D., Botstein, D., and Alani, E. (2006). Accumulation of recessive lethal mutations in S. cerevisiae mlh1 mismatch repair mutants is not associated with gross chromosomal rearrangements. Genetics 174, 519-523.

Lee, S. D., Surtees, J. A., and Alani, E. (2007). Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding Domain I in mismatch recognition. J. Mol. Biol. 366, 53-66.

Wanat, J. J., Singh, N., and Alani, E. (2007). The effect of genetic background on the function of Saccharomyces cerevisiae mlh1 alleles that correspond to HNPCC missense mutations. Hum. Mol. Genet. 16, 445-452.

Gorman, J., Chowdhury, A., Surtees, J. A., Shimada, J., Reichman, D. R., Alani, E., and Greene, E. (2007) Dynamic basis for one-dimensional DNA scanning by the mismatch repair complex Msh2-Msh6. Mol. Cell 28, 359-370.

Nishant, K.T., Plys, A., and Alani, E. (2008) A mutation in the putative MLH3 endonuclease domain confers a defect in both mismatch repair and meiosis in Saccharomyces cerevisiae.
Genetics 179, 747-755.

Demogines, A., Wong, A., Aquadro, C., and Alani, E. (2008) Incompatibilities involving yeast mismatch repair genes: a role for genetic modifiers and implications for disease penetrance and variation in genomic mutation rates. PLoS Genetics 4, e1000103.

Demogines, A., Smith, E., Kruglyak, L., and Alani, E. (2008) Identification and dissection of a complex DNA repair sensitivity phenotype in baker's yeast. PLoS Genetics 4, e1000123.

Lyndaker, A.M., Goldfarb, T., and Alani, E. (2008) Mutants defective in Rad1-Rad10-Slx4 exhibit a unique pattern of viability during mating type switching in S. cerevisiae. Genetics 179, 1807-1821.

Wanat, J., Kim, K., P., Kozul, R., Zanders, S., Weiner, B., Kleckner, N., and Alani, E. (2008) Csm4, in collaboration with Ndj1, mediates telomere-led chromosome dynamics and recombination during yeast meiosis. PLoS Genetics, in press.