About the Project
Correct chromosome partitioning during meiosis is achieved through a series of complex changes at the level of DNA molecules, chromosome structure and nuclear organization. These include: The assembly of axial elements containing cohesin, the complex that provides sister chromatid cohesion (SCC), pairing of homologous chromosomes, the assembly of a proteinaceous scaffold (the synaptonemal complex, SC) between the homologues, and the formation of crossover recombination events between DNA molecules of paired homologues. Inter-homologue crossovers, together with SCC, provide the basis of chiasmata, temporary physical links that hold homologues together following disassembly of the SC during late meiotic prophase. Then, the two-step release of SCC during the meiotic divisions allows the segregation of the homologues on the first meiotic spindle, followed by the partition of sister chromatids during meiosis II. Defects in crossover formation or SCC release result in the formation of aneuploid gametes, a leading cause of miscarriages and birth defects in humans.
Our main aim is to understand the molecular mechanisms that promote the correct execution and coordination of the different chromosomal events of the meiotic program. We are using C. elegans as an experimental organism and a combination of different experimental approaches including: genetics, biochemistry, molecular biology, three-dimensional microscopy and live imaging of meiotic chromosomes. Worms are especially well suited for the study of meiosis since germ cells comprise more than half of the cells in adult worms, and they are arranged in the gonad in a clear temporal/spatial gradient that correlates with the sequential stages of meiosis. The main goal of the project will be to investigate how proteins that bind to meiotic chromosomes, such as HORMA-domain proteins and cohesin, promote the completion of key meiotic events and contribute to regulate gene expression in the germ line.
References
Crawley, O., Barroso, C., Testori, S., Ferrandiz, N., Silva, N., Castellano-Pozo, M., Jaso-Tamame, A.L., and Enrique Martinez-Perez (2016). Cohesin-interacting protein WAPL-1 regulates meiotic chromosome structure and cohesion by antagonizing specific cohesin complexes. eLife, 5: e10851.
Silva N, Ferrandiz N, Barroso C, Tognetti S, Lightfoot J, Telecan O, Encheva V, Faull P, Hanni S, Furger A, Snijders AP, Speck C and Martinez-Perez (2014). The Fidelity of Synaptonemal Complex Assembly Is Regulated by a Signaling Mechanism that Controls Early Meiotic Progression. Dev Cell, 31: 503–511.
Labrador L, Barroso C, Lightfoot J, Müller-Reichert T, Flibotte S, Taylor J, Moerman DG, Villeneuve AM, Martinez-Perez E. (2013). Chromosome movements promoted by the mitochondrial protein SPD-3 are required for homology search during Caenorhabditis elegans meiosis. PLoS Genet 9 (5): e1003497.
Lightfoot, J., Testori, S., Barroso, C., and E. Martinez-Perez (2011). Loading of meiotic cohesin by SCC-2 is required for activation of the DNA damage checkpoint and for early processing of DSBs. Curr Biol 21: 1421-1430.
Adamo, A., Collis, S.A., Adelman, C.A., Silva, N., Horejsi, Z., Ward, J., Martinez-Perez, E., Boulton, S.J., and A. La Volpe (2010). Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Mol Cell 39: 25-35.
Ward, J.D., Muzzini, D.M., Petalcorin, M.I., Martinez-Perez, E., Martin, J.S., Plevani, P., Cassata, G., Marini, F., and Boulton, S.J. (2010). Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repair. Mol Cell 37: 259-272.
E. Martinez-Perez and Monica P. Colaiacovo (2009). Distribution of meiotic recombination events: Talking to your neighbors. Curr. Opin. Genet. Dev. 19: 105-112.