The multiple roles of the Mre11 complex for meiotic recombination

Abstract

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.

Cytological analysis of MRE11 protein during early meiotic prophase I in Arabidopsis and tomato

“…hypomorphic mre11 mutants in mammals as well as null mre11 mutants in budding yeast, Coprinus, worms, and plants have meiotic defects in synapsis, crossing over, and chromosome segregation (Gerecke and Zolan 2000;Keeney 2001;Chin and Villeneuve 2001;Bundock and Hooykaas 2002;Theunissen et al 2003;Puizina et al 2004;Cherry et al 2007;Borde 2007). MRE11 is required for meiotic DSB formation in some but not all of these organisms (reviewed by Borde 2007).…”

“…MRE11 is required for meiotic DSB formation in some but not all of these organisms (reviewed by Borde 2007). However, MRE11 is essential for later steps of meiotic recombination in all studied organisms, probably by removing SPO11 from the 5′ ends at DSB sites (Neale et al 2005).…”

“…However, MRE11 is essential for later steps of meiotic recombination in all studied organisms, probably by removing SPO11 from the 5′ ends at DSB sites (Neale et al 2005). The MRE11 complex is also proposed to play a crucial role in sensing DSBs and activating checkpoints in meiosis and in the somatic cell cycle (reviewed by Borde 2007).…”

Pairing in plants: Import is important

“…The breaks are recognized by the MRN complex, which creates ssDNA overhangs (7,8). The MRN complex is composed of MRE11, RAD50, and NBS1.…”

“…The breaks are repaired to produce cross-overs between homologous pairs or gene conversions. Knockouts of RAD50 and MRE11 in Arabidopsis lead to defects in homologue pairing, suggesting a link between pairing and recombination functions (7)(8)(9)(10)(11).…”