Crossovers direct the accurate segregation of meiotic chromosomes. Several decades of effort has led to an understanding of many aspects of the meiotic recombination pathway, especially in S. cerevisiae. Although the early steps in meiotic recombination appear to be universal, there is clear variation in the processes that actually generate crossovers. A thorough understanding of meiotic recombination will therefore require studies in multiple model systems. This proposal takes advantage of features of Drosophila melanogaster that make certain experiments possible that are not possible in other model organisms. We will map the structures of recombination intermediates and products at high resolution by preserving heteroduplex DNA with dense marker spacing. We will also analyze both products of reciprocal crossovers to map gene conversion tracts. To better understand crossover control, we will test hypotheses for functions of a set of genes that encode MCM-like proteins essential for crossover formation, using a combination of genetic, biochemical, and cytological approaches. Finally, we will also study the late stages of the recombination process. Having identified a major Holliday junction resolvase complex, we will now ask whether other putative resolvases play a role in generating meiotic crossovers. These experiments will illuminate previously unknown features of meiotic recombination and further our understanding of the degree to which different species have selected alternative branches of DNA repair pathways to effect meiotic recombination.

Public Health Relevance

Meiosis is a specialized cell division that is used to make specialized cells, such as eggs, sperm, or spores that allow sexual reproduction. Recombination - the exchange of DNA between maternal and paternal chromosomes - is a crucial part of meiosis. This project seeks to better understand the complex mechanisms of DNA recombination, through genetic, cytological, and biochemical experiments that use the fruit fly as a model organism.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular Genetics C Study Section (MGC)
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Hagan, Ann A
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University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
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Holsclaw, Julie Korda; Sekelsky, Jeff (2017) Annealing of Complementary DNA Sequences During Double-Strand Break Repair in Drosophila Is Mediated by the Ortholog of SMARCAL1. Genetics 206:467-480
Hatkevich, Talia; Kohl, Kathryn P; McMahan, Susan et al. (2017) Bloom Syndrome Helicase Promotes Meiotic Crossover Patterning and Homolog Disjunction. Curr Biol 27:96-102
Crown, K Nicole; McMahan, Susan; Sekelsky, Jeff (2014) Eliminating both canonical and short-patch mismatch repair in Drosophila melanogaster suggests a new meiotic recombination model. PLoS Genet 10:e1004583
Kuo, H Kenny; McMahan, Susan; Rota, Christopher M et al. (2014) Drosophila FANCM helicase prevents spontaneous mitotic crossovers generated by the MUS81 and SLX1 nucleases. Genetics 198:935-45
LaFave, Matthew C; Andersen, Sabrina L; Stoffregen, Eric P et al. (2014) Sources and structures of mitotic crossovers that arise when BLM helicase is absent in Drosophila. Genetics 196:107-18
Kohl, Kathryn P; Sekelsky, Jeff (2013) Meiotic and mitotic recombination in meiosis. Genetics 194:327-34
Lake, Cathleen M; Holsclaw, Julie Korda; Bellendir, Stephanie P et al. (2013) The development of a monoclonal antibody recognizing the Drosophila melanogaster phosphorylated histone H2A variant (?-H2AV). G3 (Bethesda) 3:1539-43
McMahan, Susan; Kohl, Kathryn P; Sekelsky, Jeff (2013) Variation in meiotic recombination frequencies between allelic transgenes inserted at different sites in the Drosophila melanogaster genome. G3 (Bethesda) 3:1419-27
Crown, K Nicole; Sekelsky, Jeff (2013) Targeted gene replacement in Drosophila goes the distance. Genetics 193:377-81
Kohl, Kathryn P; Jones, Corbin D; Sekelsky, Jeff (2012) Evolution of an MCM complex in flies that promotes meiotic crossovers by blocking BLM helicase. Science 338:1363-5

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