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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 Mehrotra, S. and K.S. McKim, 2006 Temporal Analysis of Meiotic DNA
Double-Strand Break Formation and Repair in Drosophila Females PLoS
Cesario, J., B. Redding, N. Shah, T. Rahman, J.K. Jang and K. S. McKim,
2006 Subito, a Kinesin 6 family member, participates in mitotic spindle
assembly and interacts with mitotic regulators such as Polo kinase and
the Passenger proteins. J. Horner, V.L., Z. Czank, J.K. Jang, N. Singh, B.C. Williams, J. Puro, E.
Kubli, S.D. Hanes, K.S. McKim, M.F. Wolfner, and M.L. Goldberg, 2006 The
Drosophila Calcipressin Sarah is Required for Several Aspects of Egg
Activation. Gong, W.J, K.S. McKim and R.S. Hawley RS, 2005 All Paired Up with No
Place to Go: Pairing, Synapsis, and DSB Formation in a Balancer
Heterozygote. McKim, K.S., 2005 When Size Does Not Matter: Pairing Sites during
Meiosis. Jang, J.K., T. Rahman and K. S. McKim, 2005 The kinesinlike protein subito contributes to central spindle assembly and organization of the meiotic spindle in Drosophila oocytes. Mol. Biol. Cell.: 16:4684-4694 Dorsett D., J.C. Eissenberg, Z. Misulovin, A. Martens, B. Redding and K.S. McKim, 2005 Effects of sister chromatid cohesion proteins on cut gene expression during wing development in Drosophila. Development: 132:4743-4753 Anderson, L.K., S.M. Royer, S.L. Page, K.S. McKim, A. Lai, M.A. Lilly
and R.S. Hawley, 2005 Juxtaposition of C(2)M and the transverse
filament protein C(3)G within the central region of Drosophila
synaptonemal complex. Sherizen, D. E., J.K. Jang, N. Kato, and K. S. McKim, 2005 Translocations are dominant meiotic crossover suppressors due to a defect early in the recombination pathway. Genetics: 169: 767-81 R. Bhagat, E. A. Manheim, D. E. Sherizen and K. S. McKim, 2004 Studies on crossover specific mutants and the distribution of crossing over in Drosophila females. Cytogenet Genome Res 107: 160-171 J.K. Jang, Sherizen, D.E., R. Bhagat, E.A. Manheim and Kim S. McKim, 2003 Relationship of DNA double-strand breaks to synapsis in Drosophila. J. Cell Science 116: 3069-3077 Manheim E. A. and K. S. McKim, 2003 C(2)M, a novel component of the synaptonemal complex, regulates meiotic crossing over. Curr. Biol. 13: 276-285 McKim, K.S., E.A. Manheim and J.K. Jang 2002 Meiotic recombination and chromosome segregation in Drosophila females, Annu. Rev. Genet. 36: 205- 232 Liu, H., J.K. Jang, N. Kato and K. S. McKim, 2002 mei-P22 encodes a chromosome-associated protein required for the initiation of meiotic recombination in Drosophila melanogaster. Genetics 162: 245-258 Guinta, K., J.K. Jang, E.A Manheim, G. Subramanian and K. S. McKim, 2002 subito encodes a kinesin-like protein required for meiotic spindle pole formation in Drosophila melanogaster. Genetics 160: 1489-1501 Manheim, E.A. J. K. Jang and K. S. McKim, 2002 Cytoplasmic localization and regulation of MEI-218, a protein required for meiotic crossing over in Drosophila. Mol. Biol. Cell 13: 84-95 Liu, H., J.K. Jang, J. Graham, K. Nycz, K. and K.S. McKim, 2000 Two
genes required for meiotic recombination are expressed from a
dicistronic message. Page, S.L., K.S. McKim, B. Deneen, T. L. Van Hook, and R. S. Hawley, 2000 Genetic studies of mei-P26 reveal a link between the processes that control germ cell proliferation in both sexes and those that control meiotic exchange in Drosophila. Genetics 155:1757-72 McKim, K.S., J.K. Jang, J.J. Sekelsky, A. Laurencon, and R. S. Hawley,
2000 mei-41 is required for precocious anaphase in Drosophila females.
Sekelsky, J.J., K. S. McKim, L. Messina, R.L. French, W.D Hurley, T. Arbel, G.M. Chin, B. Deneen, S.J. Force, K.L. Hari, J.K. Jang, A.C. Laurencon, L.D. Madden, H.J. Matthies, D.B. Milliken, S.L. Page, A.D. Ring, S.M. Wayson, C.C. Zimmerman and R.S. Hawley, 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., B. Green-Maroquin, G. Chin, J. J. Sekelsky and R. S. Hawley, 1998 Meiotic Synapsis in the Absence of Recombination. Science 279: 876-878. McKim, K.S., J.B Dahmus and R.S. Hawley, 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 R.S. Hawley, 1995 Chromosomal control of meiotic cell division. Science 270: 1595-1601. Lab Support Janet Jang, Laboratory Researcher Rajal Patel, Laboratory Techician Hao Liu, Graduate Fellow Elizabeth Manheim, Graduate Fellow |
Research
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