Résumés
Résumé
La recombinaison méiotique correspond à des échanges réciproques de matériel génétique entre les chromosomes homologues maternels et paternels. Ces échanges sont nécessaires à la ségrégation correcte des chromosomes homologues lors de la première division méiotique. Les homologues des protéines MutS (protéines MSH) et MutL (protéines MLH et PMS) d’Escherichia coli, initialement étudiés dans le cadre de la réparation des mésappariements de l’ADN, sont également impliqués dans la recombinaison méiotique. Dans ces deux fonctions, un hétérodimère de protéines homologues de MutS interagit avec un autre hétérodimère composé d’homologues de MutL. Nous avons contribué à déterminer la composition de ces hétérodimères, étape indispensable à la définition du rôle joué par ces protéines au cours de la méiose chez les mammifères. Nos résultats permettent de proposer qu’une des fonctions des homologues de MutS et de MutL serait de détecter des mésappariements présents au niveau des intermédiaires de recombinaison afin d’éviter des échanges « illégitimes » entre des régions d’ADN non homologues au cours de la méiose.
Summary
In eukaryotes, homologs of the Escherichia coli MutS and MutL proteins are crucial for both meiotic recombination and post-replicative DNA mismatch repair. Both pathways require the formation of a MutS homolog complex which interacts with a second heterodimer, composed of two MutL homologs. During mammalian meiosis, it is likely that chromosome synapsis requires the presence of a MSH4-MSH5 heterodimer. PMS2, a MutL homolog, seems to play an important role in this process. A MSH4-MSH5 heterodimer is also likely present later with other MutL homologs (MLH1 and MLH3) and is involved in the crossing-over process. The phenotype of msh4-/-mutant mice and MSH4 immunolocalization on meiotic chromosomes suggest that MSH4 has an early function in mammalian meiotic recombination. Both MSH4 and PMS2 directly interact with the RAD51 DNA strand exchange protein. In addition, MSH4 and RAD51 proteins co-localize on mouse meiotic chromosome cores. These results suggest that MSH4 and its partners could act, just after strand exchange promoted by RAD51, to check the homology of DNA heteroduplexes.
Parties annexes
Références
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