A genetic analysis of the Drosophila mcm5 gene defines a domain specifically required for meiotic recombination.
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 mcm5(A7)) that specifically impairs the meiotic recombination process. We demonstrate that the decrease in recombination observed in females homozygous for mcm5(A7) 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 mcm5(A7) 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.
Lake
Cathleen M
CM
Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA. cml@stowers-institute.org
Teeter
Kathy
K
Page
Scott L
SL
Nielsen
Rachel
R
Hawley
R Scott
RS
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair; D004330:Drosophila / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D017344:Genes, Insect; D006720:Homozygote; D008297:Male; D008540:Meiosis / Q000235:genetics; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D011995:Recombination, Genetic
D018797:Cell Cycle Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; C489426:Mcm5 protein, Drosophila