REC, a new member of the MCM-related protein family, is required for meiotic recombination in Drosophila.

Abstract

rec mutations result in an extremely low level of recombination and a high frequency of primary non-disjunction in the female meiosis of Drosophila melanogaster . Here we demonstrate that the rec gene encodes a novel protein related to the mini-chromosome maintenance (MCM) proteins. Six MCM proteins (MCM2 -7) are conserved in eukaryotic genomes, and they function as heterohexamers in the initiation and progression of mitotic DNA replication. Three rec alleles, rec 1 , rec 2 and rec 3 , were found to possess mutations within this gene, and P element-mediated germline transformation with a wild-type rec cDNA fully rescued the rec mutant phenotypes. The 885 amino acid REC protein has an MCM domain in the middle of its sequence and, like MCM2, 4, 6 and 7, REC contains a putative Zn-finger motif. Phylogenetic analyses revealed that REC is distantly related to the six conserved MCM proteins. Database searches reveal that there are candidates for orthologs of REC in other higher eukaryotes, including human. We addressed whether rec is involved in DNA repair in the mitotic division after the DNA damage caused by methylmethane sulfonate (MMS) or by X-rays. These analyses suggest that the rec gene has no, or only a minor, role in DNA repair and recombination in somatic cells.

A Genetic Analysis of the Drosophilamcm5Gene Defines a Domain Specifically Required for Meiotic Recombination

“…The reduction in exchange is most severe in the two regions (cv-v and v-f ) that show the highest levels of exchange in control females. Similar patterns of exchange reduction are also observed in females homozygous for either of two other meiotic mutants, rec/mcm8 and mei-218, both of which define genes that encode MCM or MCM domain-containing proteins (Matsubayashi and Yamamoto 2003;Blanton et al 2005;J. Sekelsky and K. McKim, personal communication).…”

“…There was no difference in number of progeny produced from mock and 0.8% MMS-treated embryos at either time point (data not shown), indicating that the inability to repair DSBs into crossover products is due to a defect in the meiotic recombination pathway and not to a general inability to repair DNA lesions. Therefore, it appears that all three MCMcontaining genes (mei-218, rec/mcm8, and mcm5) that show reduced levels of meiotic exchange are all proficient in somatic DNA repair (Baker et al 1978;Matsubayashi and Yamamoto 2003;Blanton et al 2005).…”

Addressing the Enigma of MCM8 in DNA Replication

“…Which MCM partners MCM8 might act with functionally is presently not known. Studies in Drosophila point to a role in meiotic recombination (Matsubayashi & Yamamoto, 2003) and at the repair synthesis step in meiosis crossover (Blanton et al, 2005). Future studies should address whether there is a similar role for MCM8 in other species or whether this is a specific function of Drosophila MCM8 brought about by sequence divergence.…”

“…A similar region is missing in Dm MCM8. This deletion most likely does not eliminate DNA binding because Dm MCM8 is reportedly involved in DNA repair synthesis in meiosis (Matsubayashi & Yamamoto, 2003;Blanton et al, 2005). Based on archaeon MtMCM mutational analysis, N-and C-terminal sequences were found to play a regulatory role in ATP hydrolysis with effects on substrate binding and on processivity (Jenkinson & Chong, 2006).…”

“…Following the first two reports identifying human MCM8, the Drosophila rec gene was identified as a new member of the MCM family and was reported to be required for meiotic recombination in this species (Matsubayashi & Yamamoto, 2003). This group recognized the MCM domain and the putative Zn-finger motif through comparison with MCM2-7.…”