Meiosis and recombination
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Institute of Human Genetics (IGH) UMR 9002, Université de Montpellier
141 rue de la Cardonille
Montpellier – France
Scientific Interest
In sexually reproducing species, meiosis allows the formation of haploid gametes from diploid cells. The halving of the DNA content results from a specialized cell cycle, where a single phase of DNA replication is followed by two divisions. The reductional segregation of homologous chromosomes (homologues) at the first meiotic division requires the establishment of connections between homologues. In most species, these connections are established during a long and specialized prophase by reciprocal exchanges between homologues. These exchanges, also called crossing over, result from a highly regulated homologous recombination pathway that drives the recognition and interaction between homologues and the formation of at least one crossing over per homologue pair. Crossovers also generate new allele combinations and thus increase genetic diversity and contribute to genome evolution. The absence of crossover leads to chromosome segregation defects and sterility, and alteration of the meiotic recombination pathway can lead to genome rearrangements and aneuploidy. Our team is investigating several aspects of the mechanism and regulation of meiotic recombination and its evolutionary implication using the mouse as a model system. Meiotic recombination events are initiated by the formation of DNA double-strand breaks (DSBs, several hundred per nucleus in mice), the repair of which leads to both crossovers and non-crossovers (gene conversion without crossover). The main steps and factors involved in this pathway are evolutionary conserved. A thematic newly developed in our team is the regulation of DSB formation and repair within transposable elements (TEs). These homologous sequences scattered within the genome represent an additional challenge for the maintenance of genome integrity during homologous recombination. Indeed, any DSB occurring within a TE renders the choice of the repair template critical, because of its chance to be repaired by non-allelic homologous recombination. We thus try to understand how meiotic recombination copes with TEs.
In sexually reproducing species, meiosis allows the formation of haploid gametes from diploid cells. The halving of the DNA content results from a specialized cell cycle, where a single phase of DNA replication is followed by two divisions. The reductional segregation of homologous chromosomes (homologues) at the first meiotic division requires the establishment of connections between homologues. In most species, these connections are established during a long and specialized prophase by reciprocal exchanges between homologues. These exchanges, also called crossing over, result from a highly regulated homologous recombination pathway that drives the recognition and interaction between homologues and the formation of at least one crossing over per homologue pair. Crossovers also generate new allele combinations and thus increase genetic diversity and contribute to genome evolution. The absence of crossover leads to chromosome segregation defects and sterility, and alteration of the meiotic recombination pathway can lead to genome rearrangements and aneuploidy. Our team is investigating several aspects of the mechanism and regulation of meiotic recombination and its evolutionary implication using the mouse as a model system. Meiotic recombination events are initiated by the formation of DNA double-strand breaks (DSBs, several hundred per nucleus in mice), the repair of which leads to both crossovers and non-crossovers (gene conversion without crossover). The main steps and factors involved in this pathway are evolutionary conserved. A thematic newly developed in our team is the regulation of DSB formation and repair within transposable elements (TEs). These homologous sequences scattered within the genome represent an additional challenge for the maintenance of genome integrity during homologous recombination. Indeed, any DSB occurring within a TE renders the choice of the repair template critical, because of its chance to be repaired by non-allelic homologous recombination. We thus try to understand how meiotic recombination copes with TEs.
Thematic