David Kaback, Ph.D.
Meiotic Pairing and Chromosome Segregation
Meiosis is the specialized form of cell division used for producing haploid gametes such as sperm and eggs. In humans, defective meiotic divisions can cause Downs, Turner and Klinefelter syndromes and spontaneous miscarriages. During meiosis, homologous chromosomes pair, undergo recombination and then segregate from each other reducing the chromosome number by half. Recombination between each pair of homologous chromosomes is essential for their proper segregation. We are studying mechanisms that ensure recombination between each pair of homologous chromosomes and have found that recombination rates respond directly to chromosome size; Small chromosomes recombine more per base pair of DNA than large chromosomes. This size-dependent control appears to function by preferentially inducing crossovers near chromosome ends or preferentially inhibiting recombination on larger chromosomes that have already undergone recombination; a process termed crossover interference. This finding has led to our investigation of the molecular mechanism of crossover interference, a process that affects large parts of whole chromosomes. We currently are trying to determine where recombination is initiated on whole chromosomes. These studies involve studying the meiotic synaptonemal complex (SC), a structure that forms when homologous chromosomes undergo recombination. We have produced fluorescent SCs and are using them to visualize the dynamics of the meiotic pairing process in live meiotic cells.
Finally, we are investigating the function of subtelomeric heterochromatin in meiotic pairing. Our studies have revealed that these chromosomal regions act as a barrier to meotic recombination and this barrier ensures that recombination occurs in chromosomal regions where recombination can promote chromosome segregation. Current studies are aimed at determining the mechanism of the inhibition of recombination.
- Barton, A. B., Pekosz, M., Kurvathi, R. S. and Kaback, D.B. (2008) Meiotic recombination at the ends of chromosomes in Saccharomyces cerevisiae. Genetics 179: 1221-1235.
- Scherthan, H., Wang, H., Adelfalk, C., White, E. J., Cowan, C., Cande, W. Z. and Kaback, D.B. (2007) Chromosome mobility during meiotic prophase in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 104: 16934-16939.
- Barton, A. B., Su, Y., Lamb, J., Barber, D. and Kaback, D.B. (2003) A function for subtelomeric DNA in Saccharomyces cerevisiae. Genetics, 165: 929-934.
- Kaback, D.B., Barber, D., Mahon, J., Lamb, J. and You, J., 1999, Chromosome size-dependent control of meiotic reciprocal recombination in Saccharomyces cerevisiae: The role of crossover interference. Genetics 152:1475-1486.
- Loidl, J., Scherthan, H. and Kaback, D.B., 1994, Physical Association of nonhomologous chromosomes precedes distributive disjunction in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. 91:331-334.
- Kaback, D.B., Guacci, V., Barber, D. and Mahon, J., 1992, Chromosome size-dependent control of meiotic recombination. Science 256:228-232.
* Full list of publications on PubMed
Training and Positions
1971 B.S. in Biology, State University of New York at Stony Brook, NY
1976 Ph.D. in Biology, Brandeis University, Waltham, MA
1976-1979 Postdoctoral Research, California Institute of Technology, Pasadena, CA