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Originally published as Genetics Published Articles Ahead of Print on June 11, 2007.

Genetics, Vol. 176, 2151-2163, August 2007, Copyright © 2007
doi:10.1534/genetics.107.073551

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A Genetic Analysis of the Drosophila mcm5 Gene Defines a Domain Specifically Required for Meiotic Recombination

Cathleen M. Lake*,1, Kathy Teeter*, Scott L. Page{dagger}, Rachel Nielsen* and R. Scott Hawley*,{ddagger}

* Stowers Institute for Medical Research, Kansas City, Missouri 64110, {dagger} Comparative Genomics Centre, James Cook University, Townsville, 4811 Australia and {ddagger} Department of Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160

1 Corresponding author: Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, MO 64110.
E-mail: cml{at}stowers-institute.org

Members of the minichromosome maintenance (MCM) family have pivotal roles in many biological processes. Although originally studied for their role in DNA replication, it is becoming increasingly apparent that certain members of this family are multifunctional and also play roles in transcription, cohesion, condensation, and recombination. Here we provide a genetic dissection of the mcm5 gene in Drosophila that demonstrates an unexpected function for this protein. First, we show that homozygotes for a null allele of mcm5 die as third instar larvae, apparently as a result of blocking those replication events that lead to mitotic divisions without impairing endo-reduplication. However, we have also recovered a viable and fertile allele of mcm5 (denoted mcm5A7) that specifically impairs the meiotic recombination process. We demonstrate that the decrease in recombination observed in females homozygous for mcm5A7 is not due to a failure to create or repair meiotically induced double strand breaks (DSBs), but rather to a failure to resolve those DSBs into meiotic crossovers. Consistent with their ability to repair meiotically induced DSBs, flies homozygous for mcm5A7 are fully proficient in somatic DNA repair. These results strengthen the observation that members of the prereplicative complex have multiple functions and provide evidence that mcm5 plays a critical role in the meiotic recombination pathway.


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Genetics 2007 176: NP. [Full Text]  



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