mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved

Abstract

Meiotic recombination requires the action of several gene products in both Saccharomyces cerevisiae and Drosophila melanogaster. Genetic studies in D. melanogaster have shown that the mei-W68 gene is required for all meiotic gene conversion and crossing-over. We cloned mei-W68 using a new genetic mapping method in which P elements are used to promote crossing-over at their insertion sites. This resulted in the high-resolution mapping of mei-W68 to a <18-kb region that contains a homolog of the S. cerevisiae spo11 gene. Molecular analysis of several mutants confirmed that mei-W68 encodes an spo11 homolog. Spo11 and MEI-W68 are members of a family of proteins similar to a novel type II topoisomerase. On the basis of this and other lines of evidence, Spo11 has been proposed to be the enzymatic activity that creates the double-strand breaks needed to initiate meiotic recombination. This raises the possibility that recombination in Drosophila is also initiated by double-strand breaks. Although these homologous genes are required absolutely for recombination in both species, their roles differ in other respects. In contrast to spo11, mei-W68 is not required for synaptonemal complex formation and does have a mitotic role.

Differential gene expression of mammalian SPO11/TOP6A homologs during meiosis1

“…Although this structural similarity is consistent with a role for SPO11 as the enzyme that catalyzes meiosis-speci¢c DSBs, enzymatic activity for yeast or other eukaryotic SPO11 proteins has not been demonstrated. Sequence homology with the SPO11 gene product and similar function in meiosis has been noted in rec12 of ¢ssion yeast [8], £y MEI-W68 [9] and worm Spo-11 [10], indicating that the underlying mechanism of meiotic recombination is likely to be highly conserved among eukaryotes. However, unlike the situation for budding yeast, chromosome synapsis is not impaired in the mei-W68 and spo-11 mutants.…”

Double-stranded DNA breaks and gene functions in recombination and meiosis

“…This tyrosine residue is conserved in the SPO11 protein and is critical for its function [20]. Moreover, SPO11 homologs have been found in a wide range of organisms, including Arabidopsis thaliana, Caenorhabditis elegans, D. melanogaster, Coprinus cinereus, and mammals, indicating that this SPO11-catlayzed DSB generation is a conserved process among organisms [21][22][23][24][25][26][27][28]. Although the biochemical activity of SPO11 has not yet been determined, mutations in genes required for meiotic DSB repair result in chromosome fragmentation.…”

“…However, in Drosophila and C. elegans spo11 mutants, although meiotic recombination is defective, formation of synaptonemal complexes were observed independent of SPO11 function [21,22]. Interestingly, the Drosophila SPO11 homolog, MEI-W68, has a function in mitotic recombination.…”

SPO11 : une activité de coupure de l’ADN indispensable à la méiose

“…L'analyse des mutants des gènes correspondant à ces homologues a été réalisée par des méthodes différentes selon les organismes étudiés: test de fertilité, analyse cellulaire de la différenciation, analyse cytologique, ou encore analyse génétique et moléculaire de la recombinaison (Tableau I). Les résultats révèlent plusieurs caractéristiques communes aux différentes espèces étudiées [13][14][15][16][17][18][19]20]. La fertilité est réduite ou nulle chez tous les mutants spo11 (délétion ou interruption du gène).…”