Publications

Book Chapter
Mehrotra, S, Hawley RS, McKim KS.  2007.  Synapsis, double strand breaks and domains of crossover control in females. Recombination and meiosis, crossing-over and disjunction . :125-152.
Journal Article
McKim, KS, Jang JK, Sekelsky JJ, Laurencon A, Hawley RS.  2000.  mei-41 is required for precocious anaphase in Drosophila females. Chromosoma. 109:44-49.
Hari, KL, Santerre A, Sekelsky JJ, McKim KS, Boyd JB, Hawley RS.  1995.  The mei-41 gene of D. melanogaster is a structural and function homolog of the human ataxia telangiectasia gene. Cell. 82:815-821.
McKim, KS, Hayashi-Hagihara A.  1998.  mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved. Genes & Dev.. 12:2932-42. AbstractWebsite
Meiotic recombination requires the action of several gene products in both Saccharomyces cerevisiae and Drosophila melanogaster. Genetic studies in D. melanogaster have shown that the mei-W68 gene is required for all meiotic gene conversion and crossing-over. We cloned mei-W68 using a new genetic mapping method in which P elements are used to promote crossing-over at their insertion sites. This resulted in the high-resolution mapping of mei-W68 to a 18-kb region that contains a homolog of the S. cerevisiae spo11 gene. Molecular analysis of several mutants confirmed that mei-W68 encodes an spo11 homolog. Spo11 and MEI- W68 are members of a family of proteins similar to a novel type II topoisomerase. On the basis of this and other lines of evidence, Spo11 has been proposed to be the enzymatic activity that creates the double- strand breaks needed to initiate meiotic recombination. This raises the possibility that recombination in Drosophila is also initiated by double-strand breaks. Although these homologous genes are required absolutely for recombination in both species, their roles differ in other respects. In contrast to spo11, mei-W68 is not required for synaptonemal complex formation and does have a mitotic role.
Giunta, KL, Jang JK, Manheim EM, Subramanian G, McKim KS.  2002.  subito encodes a kinesin-like protein required for meiotic spindle pole formation in Drosophila melanogaster. Genetics. 160:1489-1501.
Mathieu, J, Cauvin C, Moch C, Radford SJ, Sampaio P, Perdigoto CN, Schweisguth F, Bardin AJ, Sunkel CE, McKim K et al..  2013.  Aurora B and cyclin B have opposite effects on the timing of cytokinesis abscission in Drosophila germ cells and in vertebrate somatic cells. Dev Cell. 26(3):250-65.Website
Radford, SJ, Nguyen AL, Schindler K, McKim KS.  2016.  The chromosomal basis of meiotic acentrosomal spindle assembly and function in oocytes.. Chromosoma. Abstract
Several aspects of meiosis are impacted by the absence of centrosomes in oocytes. Here, we review four aspects of meiosis I that are significantly affected by the absence of centrosomes in oocyte spindles. One, microtubules tend to assemble around the chromosomes. Two, the organization of these microtubules into a bipolar spindle is directed by the chromosomes. Three, chromosome bi-orientation and attachment to microtubules from the correct pole require modification of the mechanisms used in mitotic cells. Four, chromosome movement to the poles at anaphase cannot rely on polar anchoring of spindle microtubules by centrosomes. Overall, the chromosomes are more active participants during acentrosomal spindle assembly in oocytes, compared to mitotic and male meiotic divisions where centrosomes are present. The chromosomes are endowed with information that can direct the meiotic divisions and dictate their own behavior in oocytes. Processes beyond those known from mitosis appear to be required for their bi-orientation at meiosis I. As mitosis occurs without centrosomes in many systems other than oocytes, including all plants, the concepts discussed here may not be limited to oocytes. The study of meiosis in oocytes has revealed mechanisms that are operating in mitosis and will probably continue to do so.
McKim, KS, Hawley RS.  1995.  Chromosomal control of meiotic cell division. Science. 270:1595-1601.
Radford, SJ, Jang JK, McKim KS.  2012.  The Chromosomal Passenger Complex is required for Meiotic Acentrosomal Spindle Assembly and Chromosome Bi-orientation. Genetics. 192:417-429. AbstractWebsite
During meiosis in the females of many species, spindle assembly occurs in the absence of the microtubule-organizing centers called centrosomes. In the absence of centrosomes, the nature of the chromosome-based signal that recruits microtubules to promote spindle assembly as well as how spindle bipolarity is established and the chromosomes orient correctly towards the poles is not known. To address these questions, we focused on the chromosomal passenger complex (CPC). We have found that the CPC localizes in a ring around the meiotic chromosomes that is aligned with the axis of the spindle at all stages. Using new methods which dramatically increase the effectiveness of RNAi in the germline, we show that the CPC interacts with Drosophila oocyte chromosomes and is required for the assembly of spindle microtubules. Furthermore, chromosome bi-orientation and the localization of the central spindle kinesin-6 protein Subito, which is required for spindle bipolarity, depend on the CPC components Aurora B and Incenp. Based on these data we propose that the ring of CPC around the chromosomes regulates multiple aspects of meiotic cell division including spindle assembly, the establishment of bipolarity, the recruitment of important spindle organization factors, and the bi-orientation of homologous chromosomes.
McKim, KS, Rose AM.  1990.  Chromosome I duplications in Caenorhabditis elegans. Genetics. 124:115-32.Website
Radford, SJ, Go A MM, McKim KS.  2016.  Cooperation Between Kinesin Motors Promotes Spindle Symmetry and Chromosome Organization in Oocytes.. Genetics. Abstract
The oocyte spindle in most animal species is assembled in the absence of the microtubule-organizing centers called centrosomes. Without the organization provided by centrosomes, acentrosomal meiotic spindle organization may rely heavily on the bundling of microtubules by kinesin motor proteins. Indeed, the minus-end directed kinesin-14 NCD and the plus-end directed kinesin-6 Subito are known to be required for oocyte spindle organization in Drosophila melanogaster How multiple microtubule-bundling kinesins interact to produce a functional acentrosomal spindle is not known. In addition, there have been few studies on the meiotic function of one of the most important microtubule-bundlers in mitotic cells, the kinesin-5 KLP61F. We have found that the kinesin-5 KLP61F is required for spindle and centromere symmetry in oocytes. The asymmetry observed in the absence of KLP61F depends on NCD, the kinesin-12 KLP54D, and the microcephaly protein ASP. In contrast, KLP61F and Subito work together in maintaining a bipolar spindle. We propose that the prominent central spindle, stabilized by Subito, provides the framework for the coordination of multiple microtubule-bundling activities. The activities of several proteins, including NCD, KLP54D, and ASP, generate asymmetries within the acentrosomal spindle, while KLP61F and Subito balance these forces resulting in the capacity to accurately segregate chromosomes.
McKim, KS, Joyce EF, Jang JK.  2009.  Cytological analysis of meiosis in fixed Drosophila ovaries. Methods Mol Biol. 558:197-216. AbstractWebsite
Methods are described to analyze two different parts of the Drosophila ovary, which correspond to early stages (pachytene) and late stages (metaphase I and beyond) of meiosis. In addition to taking into account morphology, the techniques differ by fixation conditions and the method to isolate the tissue. Most of these methods are whole mounts, which preserve the three-dimensional structure.
Manheim, EA, Jang JK, Dominic D, McKim KS.  2002.  Cytoplasmic localization and evolutionary conservation of MEI-218, a protein required for meiotic crossing over in Drosophila. Mol. Biol. Cell. 13:84-95.
Joyce, EF, Pedersen M, Tiong S, White-Brown SK, Paul A, Campbell SD, McKim KS.  2011.  Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair. J Cell Biol. 195:359-67. AbstractWebsite
Ataxia telangiectasia-mutated (ATM) and ataxia telangiectasia-related (ATR) kinases are conserved regulators of cellular responses to double strand breaks (DSBs). During meiosis, however, the functions of these kinases in DSB repair and the deoxyribonucleic acid (DNA) damage checkpoint are unclear. In this paper, we show that ATM and ATR have unique roles in the repair of meiotic DSBs in Drosophila melanogaster. ATR mutant analysis indicated that it is required for checkpoint activity, whereas ATM may not be. Both kinases phosphorylate H2AV (gamma-H2AV), and, using this as a reporter for ATM/ATR activity, we found that the DSB repair response is surprisingly dynamic at the site of DNA damage. gamma-H2AV is continuously exchanged, requiring new phosphorylation at the break site until repair is completed. However, most surprising is that the number of gamma-H2AV foci is dramatically increased in the absence of ATM, but not ATR, suggesting that the number of DSBs is increased. Thus, we conclude that ATM is primarily required for the meiotic DSB repair response, which includes functions in DNA damage repair and negative feedback control over the level of programmed DSBs during meiosis.
Horner, V.L., Czank, Z., Jang, J.K., Singh, N., Williams, B.C., Puro, J., Kubli, E., Hanes, S.D., McKim, K.S., Wolfner, M.F. et al..  2006.  The Drosophila calcipressin sarah is Required for several aspects of egg activation. Curr Biol. 16:144-6.Website
Sekelsky, JJ, McKim KS, Chin GM, Hawley RS.  1995.  The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics. 141:619-627.
Colombie, N, Cullen CF, Brittle AL, Jang JK, Earnshaw WC, Carmena M, McKim K, Ohkura H.  2008.  Dual roles of Incenp crucial to the assembly of the acentrosomal metaphase spindle in female meiosis. Development. 135:3239-46.Website
Gyuricza, MR, Manheimer KB, Apte V, Krishnan B, Joyce EF, McKee BD, McKim KS.  2016.  Dynamic and Stable Cohesins Regulate Synaptonemal Complex Assembly and Chromosome Segregation.. Current biology : CB. 26(13):1688-1698. Abstract
Assembly of the synaptonemal complex (SC) in Drosophila depends on two independent pathways defined by the chromosome axis proteins C(2)M and ORD. Because C(2)M encodes a Kleisin-like protein and ORD is required for sister-chromatid cohesion, we tested the hypothesis that these two SC assembly pathways depend on two cohesin complexes. Through single- and double-mutant analysis to study the mitotic cohesion proteins Stromalin (SA) and Nipped-B (SCC2) in meiosis, we provide evidence that there are at least two meiosis-specific cohesin complexes. One complex depends on C(2)M, SA, and Nipped-B. Despite the presence of mitotic cohesins SA and Nipped-B, this pathway has only a minor role in meiotic sister-centromere cohesion and is primarily required for homolog interactions. C(2)M is continuously incorporated into pachytene chromosomes even though SC assembly is complete. In contrast, the second complex, which depends on meiosis-specific proteins SOLO, SUNN, and ORD is required for sister-chromatid cohesion, localizes to the centromeres and is not incorporated during prophase. Our results show that the two cohesin complexes have unique functions and are regulated differently. Multiple cohesin complexes may provide the diversity of activities required by the meiotic cell. For example, a dynamic complex may allow the chromosomes to regulate meiotic recombination, and a stable complex may be required for sister-chromatid cohesion.
Dorsett, D, Eissenberg JC, Misulovin Z, Martens A, Redding B, McKim K.  2005.  Effects of sister chromatid cohesion proteins on cut gene expression during wing development in Drosophila. Development. 132:4743-53.Website