|Busch Campus Rutgers University 190 Frelinghuysen Rd. Piscataway, NJ, 08855|
The goal of the research in my lab is to understand the regulation and assembly of the mitotic and meiotic spindle and chromosome segregation. We are using genetic methods and the power of the Drosophila model system to identify and characterize proteins which play important roles in spindle assembly. While much of our work uses the meiotic acentrosomal spindle in oocytes, most of the genes and processes we are studying have important roles in mitotic spindles. For example, regulation of meiotic and mitotic cell division involves several kinases, including Aurora B, Polo and Cdk1.
I have a broad background in Genetics and Molecular biology of Drosophila with an emphasis on applying sophisticated imaging techniques. My interest in meiosis began with Graduate work in C. elegans. Starting with my post-doctoral research with Scott Hawley, I have been working in fly meiosis for almost 20 years. Past work has focused on analyzing the product of genetic screens. This has been successful and we have identified and cloned many genes by a forward genetics approach. More recently, we have been using reverse genetics and sophisticated tools in Drosophila such as site-specific mutagenesis and tissue specific RNAi to analyze the meiotic functions of several genes. The Drosophila ovary is particularly amenable to cytological analysis. Thus, we combine our genetics expertise extensively with immunoflourescence and high resolution confocal microscopy. Indeed, few labs perform the types of analysis of fixed and living oocytes that we do and we often get requests for help or collaboration. Our capabilities have expanded recently with the acquisition of a state of the art Leica SP5 confocal microscope. In addition, we are actively working with other researchers at Rutgers to obtain a system capable of super resolution (50-80nm) such as a Leica CS STED. I have the expertise, leadership and motivation necessary to successfully carry out the proposed work.
Research in my lab is directed at understanding how meiosis works. In particular, we are interested in understanding how homologous chromosomes pair and exchange genetic material during meiosis, and how this leads to the orderly segregation of the homologs at the first, or reductional, meiotic division. My laboratory studies the fruit fly Drosophila melanogaster. The emphasis of our research is on the regulation and mechanisms of meiotic recombination. Several genes have been identified which are required for the execution of meiotic recombination in Drosophila. Our analysis of these genes has placed them in a pathway defined by four major events. There are "early" genes required for either the synapsis of homlogs (c(3)G) or for the initiation of recombination (mei-P22, mei-W68). Late recombination genes are required either to determine the sites where crossovers will occur (mei-218) or for the recombination event itself (mei-9). Implied in this hypothesis is the assumption that meiotic recombination in Drosophila works through a Holliday junction. Our recent discovery that the mei-W68 gene encodes a Spo11 homolog is consistent with that hypothesis. These genes encode proteins similar to a archea-bacterial topoisomerase II. In yeast, Spo11 is believed to be responsible for creating the double strand break that initiates meiotic recombination. The question of how the genes in this pathway interact is currently under investigation in my laboratory. While we have identified important factors required for initiating meiotic recombination, very little is known about how the frequency of initiations is controlled, and the mechanism for controlling how many of these events become crossovers. These questions become even more important in light of recent data from the analysis of these genes showing that meiotic recombination in D. melanogaster is under different genetic controls than in S. cerevisiae.
Radford, S.J., J. K. Jang, and K. S. McKim, 2012 The Chromosomal Passenger Complex is required for Meiotic Acentrosomal Spindle Assembly and Chromosome Bi-orientation. Genetics: 192:417-29
Radford, S.J., A. M. Harrison, and K. S. McKim, 2012 Microtubule-depolymerizing Kinesin KLP10A Restricts the Length of the Acentrosomal Meiotic Spindle in Drosophila females. Genetics: 192:431-40
Joyce, E.F., A. Paul, K.E. Chen and K. S. McKim 2012 Multiple Barriers to Non-homologous DNA End Joining During Meiosis in Drosophila. Genetics 191: 739-46.
Joyce, E.F., M. Pedersen, S. Tiong, S.K. White-Brown, A. Paul, S. D. Campbell and K. S. McKim 2011 Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair. J. Cell Biol. 195: 359-67
Tanneti, NS., K. Landy, E. F. Joyce and K. S. McKim, 2011 A pathway for synapsis initiation during zygotene in Drosophila oocytes. Curr. Biol. 8:1852-7
Cesario, J. and K. S. McKim, 2011 RanGTP is required for meiotic spindle organization and the initiation of embryonic development in Drosophila. J. Cell Science 124:3797-810
Joyce EF, K. S. McKim, 2011 Meiotic checkpoints and the interchromosomal effect on crossing over in Drosophila females. Fly (Austin). Apr 1;5: 134-140
Orsi GA, E.F. Joyce, P. Couble, K.S. McKim and B. Loppin. 2010 Drosophila I-R hybrid dysgenesis is associated with catastrophic meiosis and abnormal zygote formation. J Cell Sci. 123: 3515 - 3524
Joyce, E. F. and K. S. McKim, 2010 Chromosome axis defects induce a checkpoint-mediated delay and interchromosomal effect on crossing over during Drosophila meiosis. Plos Genetics, 6: e1001059
McKim, K. S., E. F. Joyce and J. K. Jang, 2009 Cytological analysis of meiosis in fixed Drosophila ovaries. Methods Mol Biol 558: 197-216.
Joyce, E. F. and K. S. McKim, 2009 Drosophila PCH2 is required for a pachytene checkpoint that monitors DSB-independent events leading to meiotic crossover formation. Genetics 181: 39-51.
Joyce, E.F., N. S. Tanneti and K. S. McKim, 2009 Drosophila HDM protein is required for a subset of meiotic crossovers and interacts with repair endonuclease complex subunits MEI-9 and ERCC1. Genetics, 181:335-40
Colombie, N., C. F. Cullen, A. L. Brittle, J. K. Jang, W. C. Earnshaw, M. Carmena, K. S. McKim and H. Ohkura, 2008 Dual roles of Incenp critical to the assembly of the acentrosomal metaphase spindle in female meiosis, Development, 135:3239-46.
Wu, C., V. Singaram and K. S. McKim, 2008, mei-38 is required for chromosome segregation during meiosis in Drosophila females, Genetics, 180:61-72
Mehrotra, S., R. S. Hawley and K. S. McKim, 2007 Synapsis, double strand breaks and domains of crossover control in females, pp. 125-152 in Recombination and meiosis, crossing-over and disjunction, edited by R. Egel and D. Lankenau. Springer-Verlag, Berlin.
Jang, J.K., T. Rahman, V.S. Kober, J. Cesario and K.S. McKim 2007 Misregulation of the Kinesin-like protein Subito induces meiotic spindle formation in the absence of chromosomes and centrosomes. Genetics 177: 267-280.
Doubilet S., and K.S. McKim 2007 Spindle assembly in the oocytes of mouse and Drosophila - similar solutions to a problem. Chromosome Res. 15: 681-96.
Trowbridge K, K. McKim, S.J. Brill and J. Sekelsky, 2007 Synthetic lethality in the absence of the Drosophila MUS81 endonuclease and the DmBlm helicase is associated with elevated apoptosis. Genetics 176: 1993-2001.
McKim, K.S, 2007 Meiotic Pairing: A Place to Hook up. Curr Biol. 17:R165-8
Joyce E.F. and K.S. McKim, 2007 When specialized sites are important for synapsis and the distribution of crossovers. Bioessays 29: 217-26
Mehrotra, S. and K.S. McKim, 2006 Temporal Analysis of Meiotic DNA Double-Strand Break Formation and Repair in Drosophila Females. PLoS Genet. 2: 1883-1897
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. Cell Sci., 119: 4770-80
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. Curr Biol 16: 1441-1446
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. PLoS Genet: 1: 589 - 602
McKim, K.S., 2005 When Size Does Not Matter: Pairing Sites during Meiosis. Cell: 123(6):989-92.
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. Proc. Natl. Acad. Sci. USA: 102:4482-4487
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