title: REC, Drosophila MCM8, drives formation of meiotic crossovers.
abstract: Crossovers ensure the accurate segregation of homologous chromosomes from one another during meiosis. Here, we describe the identity and function of the Drosophila melanogaster gene recombination defective (rec), which is required for most meiotic crossing over. We show that rec encodes a member of the mini-chromosome maintenance (MCM) protein family. Six MCM proteins (MCM2-7) are essential for DNA replication and are found in all eukaryotes. REC is the Drosophila ortholog of the recently identified seventh member of this family, MCM8. Our phylogenetic analysis reveals the existence of yet another family member, MCM9, and shows that MCM8 and MCM9 arose early in eukaryotic evolution, though one or both have been lost in multiple eukaryotic lineages. Drosophila has lost MCM9 but retained MCM8, represented by REC. We used genetic and molecular methods to study the function of REC in meiotic recombination. Epistasis experiments suggest that REC acts after the Rad51 ortholog SPN-A but before the endonuclease MEI-9. Although crossovers are reduced by 95% in rec mutants, the frequency of noncrossover gene conversion is significantly increased. Interestingly, gene conversion tracts in rec mutants are about half the length of tracts in wild-type flies. To account for these phenotypes, we propose that REC facilitates repair synthesis during meiotic recombination. In the absence of REC, synthesis does not proceed far enough to allow formation of an intermediate that can give rise to crossovers, and recombination proceeds via synthesis-dependent strand annealing to generate only noncrossover products.
authors.affiliation: University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Hunter L
authors.initials: HL
authors.lastname: Blanton
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Radford
authors.forename: Susan
authors.initials: S
authors.lastname: McMahan
authors.forename: Hutton M
authors.initials: HM
authors.lastname: Kearney
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Ibrahim
authors.forename: Jeff
authors.initials: J
authors.lastname: Sekelsky
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D003433:Crosses, Genetic; D003434:Crossing Over, Genetic; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication; D004330:Drosophila / Q000166:cytology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005785:Gene Conversion; D008297:Male; D008540:Meiosis / Q000235:genetics; D016296:Mutagenesis; D011995:Recombination, Genetic; D012098:Reproduction / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C490723:REC protein, Drosophila