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Double strand break repair. genetic recombination. chromosome pairing. chromosome segregation. kinesin motor proteinsMeiotic crossing over provides a linkage between homologous chromosomes that directs their segregation at the first meiotic or reductional division. The homologous chromosomes are aligned and held together along their length by the synaptonemal complex (SC) and recombination is initiated with a double strand break (DSB). Repair of the DSBs results in either gene-conversion or crossing over. In the absence of recombination. homologous chromosomes do not segregate properly. resulting in aneuploidy and usually death of the embryo. In certain cases. these aneuploids survive; in humans. this results in syndromes such as Down's. Turner's and Klinefelter's. Research in the laboratory is directed at understanding meiosis in Drosophila melanogaster females. Our studies include several important aspects of meiotic pathway including: i) the pairing of homologous chromosomes. ii) the initiation of meiotic recombination (DSBs). iii) the repair of DSBs. and iv) the mechanism of homologous chromosomes segregation. These studies include several important and conserved genes such as Spo11. which is required to make meiotic DSBs. Rad51 homologs. which are required to repair DSBs and kinesin-like proteins. which are motor proteins that function in moving and separating chromosomes at the meiotic divisions. Many of the important genes in this process are also involved in DNA repair or the fidelity of chromosome division in other cell types. Therefore. these studies will likely provide insights into the factors affecting genome stability and cancer in mitotic cells. Selected PublicationsMcKim KS, Joyce EF, Jang JK. (2009) Cytological analysis of meiosis in fixed Drosophila ovaries. Methods Mol Biol. 558:197-216. Joyce E, Tanneti N, McKim KS. (2009) Drosophila hold'em is required for a subset of meiotic crossovers and interacts with DNA repair endonuclease complex subunits MEI-9 and ERCC1. Joyce E, McKim KS. (2008) Drosophila PCH2 is required for a Pachytene checkpoint that monitors DSB-independent events leading to meiotic crossover formation. Genetics. 181(1):39-51. Wu C, Singaram V, McKim KS. (2008) mei-38 is required for chromosome segregation during meiosis in Drosophila females. Genetics. 180(1):61-72. Doubilet S, McKim KS. (2007) Spindle assembly in the oocytes of mouse and Drosophila--similar solutions to a problem. Chromosome Res. 15(5):681-96. Review. Jang JK, Rahman T, Kober VS, Cesario J, McKim KS. (2007) Misregulation of the kinesin-like protein Subito induces meiotic spindle formation in the absence of chromosomes and centrosomes. Genetics. 177(1):267-80. Joyce EF, McKim KS. (2007) When specialized sites are important for synapsis and the distribution of crossovers. Bioessays. 29(3):217-26. Review. Cesario JM, Jang JK, Redding B, Shah N, Rahman T, McKim KS. (2006) Kinesin 6 family member Subito participates in mitotic spindle assembly and interacts with mitotic regulators. J Cell Sci. 119(Pt 22):4770-80. Horner VL, Czank A, Jang JK, Singh N, Williams BC, Puro J, Kubli E, Hanes SD, McKim KS, Wolfner MF, Goldberg ML. (2006) The Drosophila calcipressin sarah is required for several aspects of egg activation. Curr Biol. 16(14):1441-6. McKim KS. (2005) When size does not matter: pairing sites during meiosis. Cell. 123(6):989-92. Gong WJ. McKim KS. Hawley RS. (2005) All paired up with no place to go: pairing. synapsis. and DSB formation in a balancer heterozygote. PLoS Genet. 1(5):e67. Anderson LK. Royer SM. Page SL. McKim KS. Lai A. Lilly MA. Hawley RS. (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 U S A. 102(12):4482-7. Sherizen D. Jang JK. Bhagat R. Kato N. McKim KS. (2005) Meiotic recombination in Drosophila females depends on chromosome continuity between genetically defined boundaries. Genetics. 169(2):767-81. Sherizen. D. E.. Jang. J.K.. Kato. N. and McKim. K. S. (2005) Translocations are dominant meiotic crossover suppressors due to a defect early in the recombination pathway. Genetics 169: 767-81. Bhagat. R.. Manheim. E. A.. Sherizen. D. E. and McKim. K. S. (2004) Studies on crossover specific mutants and the distribution of crossing over in Drosophila females. Cytogenet Genome Res 107: 160-171 Jang. J.K.. Sherizen. D.E.. Bhagat. v. Manheim. E.A. and Kim S. McKim. K.S. (2003) Relationship of DNA double-strand breaks to synapsis in Drosophila. J. Cell Science 116: 3069-3077 Manheim. E. A. and McKim. K. S. (2003) C(2)M. a novel component of the synaptonemal complex. regulates meiotic crossing over. Curr. Biol. 13: 276-285. |
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