David Kaback, Ph.D.
Professor
Office: ICPH-E440B
Tel: 973-972-8967
Lab: ICPH-E-410A.1
Tel: 973-972-8967

NJMS Faculty Profile

Meiosis is the specialized form of cell division used diploid germ cells for producing haploid gametes such as sperm and eggs. In humans, defective meiotic divisions cause a high proportion of spontaneous miscarriages and Downs, Edwards, Turner and Klinefelter syndromes. During meiosis, the two sets of homologous chromosomes pair, undergo recombination (crossing-over), form chiasmata and then segregate from each other to opposite poles of a spindle reducing the chromosome number by half. Recombination between each pair of homologous chromosomes is essential for their proper segregation. We have studied mechanisms that ensure recombination between each pair of homologous chromosomes. We discovered that recombination rates (amount of recombination per base pair of DNA) were higher on smaller chromosomes than on large chromosomes and that recombination rates respond directly to chromosome size. This difference ensures that that even small chromosomes efficiently pair with their homologs. Chromosome sizedependent control appears to be complex and functions by preferentially initiating crossovers near chromosome ends and preferentially inhibiting recombination on larger chromosomes that have already undergone recombination; a process termed crossover interference. These findings led to our interest in the molecular mechanism of crossover interference, a process that affects large parts of whole chromosomes and is believed to require the meiotic synaptonemal complex (SC), a proteinaceous structure that forms when homologous chromosomes initiate recombination and begin to pair. The SCs continue to grow until each pair of homologous chromosomes is tightly bound together. It is believed that much recombination biochemistry is directly associated with and regulated by these structures. Therefore, we produced fluorescent SCs and used them to visualize the dynamics of the meiotic pairing process in live meiotic cells. These studies first showed that the nuclei and the paired chromosomes contained within them underwent intense movement due to an actin-dependent motor. Chromosomes were observed to oscillate between a uniform distribution and peripherally arranged arrays within each nucleus. In addition, maverick chromosomes were observed to first break free of the main chromosomal mass and then return to it. These movements have been suggested to facilitate the progress of the reactions required to complete the recombination process and to separate the partially condensed chromosomes into discrete domains to facilitate the segregation process. We furthermore suggested that the spatial association of chromosomes with the nuclear periphery might also facilitate the completion of the recombination reactions.

Finally, we investigated the function of subtelomeric heterochromatin in meiotic pairing. Our studies revealed that these chromosomal regions exhibited very low rates of recombination and therefore might act as a barrier that ensures that chiasma formation occurs at more interior regions where they can better facilitate homologous chromosome segregation. While active laboratory research is no longer being carried out, we maintain our interest in meiosis and are always willing to share reagents and protocols.

• Kaback DB. (2013) The modest beginnings of one genome project.  Genetics 194: 291-299.
  
  
• 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.

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, Department of Chemistry, California Institute of Technology, Pasadena, CA