The multiple roles of the Mre11 complex for meiotic recombination.
During the first meiotic prophase, numerous DNA double-strand breaks (DSB) are formed in the genome in order to initiate recombination between homologous chromosomes. The conserved Mre11 complex, formed of Mre11, Rad50 and Nbs1 (Xrs2 in Saccharomyces cerevisiae) proteins, plays a crucial role in mitotic cells for sensing and repairing DSB. In meiosis the Mre11 complex is also required for meiotic recombination. Depending on the organisms, the Mre11 complex is required for the formation of the DSB catalysed by the transesterase Spo11 protein. It then plays a unique function in removing covalently attached Spo11 from the 5' extremity of the breaks through its nuclease activity, to allow further break resection. Finally, the Mre11 complex also plays a role during meiosis in bridging DNA molecules together and in sensing Spo11 DSB and activating the DNA damage checkpoint. In this article the different biochemical functions of the Mre11 complex required during meiosis are reviewed, as well as the consequences of Mre11 complex inactivation for meiosis in several organisms. Finally, I describe the meiotic phenotypes of several animal models that have been developed to model hypomorphic mutations of the Mre11 complex, involved in humans in some genetic instability disorders.
Borde
Valérie
V
Institut Curie, Recombinaison et Instabilité Génétique, Centre de Recherche, UMR7147 CNRS-Institut Curie-Université P. et M. Curie, 26 rue d'Ulm, 75248, Paris Cedex 05, France. valerie.borde@curie.fr
D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D000076228:MRE11 Homologue Protein; D008540:Meiosis / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D046912:Multiprotein Complexes; D009154:Mutation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D000099257:Meiotic Recombination Protein SPO11
D045643:DNA Repair Enzymes; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D000076228:MRE11 Homologue Protein; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C121766:MRE11 protein, human; C512689:Mre11a protein, mouse; C094191:MRE11 protein, S cerevisiae; C518938:Spo11 protein, S cerevisiae; D000099257:Meiotic Recombination Protein SPO11