“Defects in meiosis lead to gametes with an incorrect number of chromosomes – this is one of the leading causes of miscarriage and birth defects in humans”
We use C. elegans as a model organism for studies spanning genetics, biochemistry and three-dimensional microscopy. Correct chromosome partitioning during meiosis is achieved through a series of complex changes at the level of DNA molecules, chromosome structure and nuclear organisation. Crucially, temporary physical links hold homologues together until they segregate from each other on the first meiotic spindle. We aim to understand how the different events of meiosis are coordinated to ensure the orderly formation of inter-homologue crossovers.
We are working to identify and study proteins involved in crossover formation. We are also studying the interplay between crossovers and meiotic chromosome structure. We have shown that crossovers trigger a remodelling of chromosome axis composition that is required for proper homologue segregation, and that HTP-1, a protein associated with the axis of meiotic chromosomes, is a key player in this remodelling process.
Association of HORMA-domain protein HTP-1 with meiotic chromosomes. Pachytene nuclei from transgenic worms expressing a wild-type HTP-1::GFP fusion protein, or an HTP-1::GFP transgene carrying the M127K mutation in HTP-1. Note that HTP-1M127K is not loaded to axial elements. However, we have observed that HTP-1M127K retains some of HTP-1 functions, demonstrating that meiotic HORMA-domain proteins play roles as nuclear soluble proteins.
Labrador L., Barroso C., Lightfoot J., Müller-Reichert T., Flibotte S., Taylor J., Moerman D.G., Villeneuve A.M., Martinez-Perez E. (2013). Chromosome movements promoted by the mitochondrial protein SPD-3 are required for homology search during Caenorhabditis elegans meiosis. PLoS Genetics, 9 (5), e1003497.
Lightfoot, J., Testori, S., Barroso, C., & Martinez-Perez, E. (2011). Loading of meiotic cohesin by SCC-2 is required for early processing of DSBs and for the DNA damage checkpoint. Current Biology, 21, 1421-1430.
Adamo, A., Collis, S. J., Adelman, C. A., Silva, N., Horejsi, Z., Ward, J. D., Martinez-Perez, E., Boulton, S. J., & La Volpe, A. (2010). Preventing nonhomologous end joining suppresses DNA repair defects of fanconi anemia. Molecular Cell, 39(1), 25–35.
Martinez-Perez, E.*, Schvarzstein, M., Barroso, C., Lightfoot, J., Dernburg, A.F., and Villeneuve, A.M., (2008). Crossovers trigger a remodeling of meiotic chromosome axis composition that is linked to two-step loss of sister-chromatid cohesion. Genes & Development, 22, 2886-2901. * Corresponding author.
Martinez-Perez, E., & Villeneuve, A. M. (2005). HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during c. elegans meiosis. Genes & Development, 19(22), 2727–2743.