Research Summary

Molecular Genetics of Meiotic Recombination

Meiotic recombination is essential for fertility in almost every sexually reproducing species. Chiasmata, which are the structures that result from meiotic crossing over, ensure the disjunction of homologous chromosomes at the reductional division by linking and orienting homologous chromosomes together on the meiosis I spindle. Compared to mitosis, meiotic recombination occurs at a very high frequency, but is precisely controlled so that one, and usually less than three, exchanges per chromosome arm per meiosis. The machinery of meiotic recombination is assembled in the recombination nodule, an organelle associated with the paired homolgous chromosomes which are held together along their entire length by a ribbon-like structure known as the synaptonemal complex (= sc). My laboratory studies D. melanogaster as a model organism to understand the mechanism of meiotic chromosome pairing, and to characterize the gene products involved in meiotic recombination. These studies employ a mix of classical genetic analysis with molecular and cell biology. We are using genetic analysis of mutants to identify most or all of the genes required for meiotic recombination. The function of the newly identified genes are then elucidated through a series of genetic and cytological tests. As we are primarily interested in the nature of the gene product, genetic mapping of each mutant facilitates cloning and molecular identification of the gene. Some of the genes which are at a more advanced stage of analysis, appear to have meiosis specific functions. For example, mei-P22 is required for all meiotic recombination and defines a crucial point at which meiotic recombination is initiated at a point after the chromosomes are fully paired. mei-218 is required for the proper assembly and appearance of the recombination nodule.

Publications

Jang, J.K., Liu, H., Graham, J., Nycz, K. and McKim, K.S. (1999) Two eukaryotic meiotic recombination genes expressed with a polycistronic message. Submitted

Sekelsky, J.J., McKim, K.S., et al. (1999) Identification of novel Drosophila meiotic genes recovered in a P-element screen. Genetics 152: 529-542.

McKim, K.S. and A. Hayashi-Hagihara (1998) mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: Evidence that the mechanism for initiating meiotic recombination is conserved. Genes & Dev. 12: 2932-2942.

McKim K.S., Green-Marroquin B.L., Sekelsky J.J., Chin G., Steinberg C., Khodosh R., Hawley R.S. (1998). Meiotic synapsis in the absence of recombination. Science. 279(5352): 876-878.

McKim, K.S., Dahmus, J.J. and Hawley,, R.S. (1996). Cloning of the Drosophila melanogaster meiotic recombination gene mei-218: A genetic and molecular analysis of interval 15E. Genetics 144: 215-228.

McKim, K.S. and Hawley, R.S. (1995). Chromosomal control of meiotic cell division. Science 270:1595-1601.

Sekelsky, J.J., McKim, K.S., Chin, G.M. and Hawley, R. Scott. (1995). The Drosophila meiotic recombination gene mei-9 encodes a homolog of the yeast excision repair protein Rad1. Genetics 141:619-627.

McKim, K. S., Jang, J.K., Theurkauf, W. and Hawley, R.S. (1993). The mechanical basis of meiotic metaphase arrest. Nature 362:364-366.

McKim, K. S., Peters, K. and Rose, A.M. (1993). Two types of sites required for meiotic chromosome pairing in Caenorhabditis elegans. Genetics 134:749-768.

Lab Support

Janet Jang, Laboratory Researcher

Janet Jang, Research Associate

Rajal Patel, Laboratory Techician

Hao Liu, Graduate Fellow

Elizabeth Manheim, Graduate Fellow