Meiosis is the specialized cell division that produces haploid gametes from diploid parental cells (gametogenesis). During meiosis, a single phase of DNA replication is followed by two consecutive rounds of chromosome segregation, resulting in the reduction of the ploidy by half. After fertilization, the normal chromosome complement is restored; therefore, the accuracy in the distribution of chromosomes to the gametes is critical for a healthy offspring and species survival. eiotic errors result in aneuploidy and, in humans, they are the main cause of pathologies associated to reproduction, leading to fertility disorders, spontaneous abortions or genetic birth defects, such as, for example, Down’s syndrome.

Meiosis involves the generation of self-inflicted DNA double-strand breaks (DSBs) on the genome of the parental germ cells. Precise recombinational repair of meiotic DSBs establishes physical connections between homologs (called chiasmata) that orchestrate their segregation during the first meiotic division. Interhomolog interactions promoting recombination are sustained by the pairing and synapsis of homologous chromosomes, and they are also facilitated by chromosome movement driven by telomere attachment to the nuclear envelope.

We are focused on the study of the surveillance mechanisms (checkpoints) that monitor proper distribution of genetic material to the progeny. This meiotic checkpoint network blocks meiotic cell cycle progression in response to recombination and/or chromosome synapsis defects, thus preventing aberrant chromosome segregation and the formation of aneuploid gametes.

We use the budding yeast Saccharomyces cerevisiae, which possesses robust meiotic quality control systems, as a major model of study. Given the evolutionary conservation of checkpoint controls, as well as the ample array of research tools available, this is an excellent model system to advance in the understanding of the molecular basis of reproductive pathologies.

Specific research lines:

1. The meiotic recombination checkpoint:
1.1 Function and regulation of the AAA+ ATPase Pch2TRIP13
1.2 Cell-cycle targets: a novel role for the polo kinase Cdc5PLK1
2. Nuclear envelope dynamics
2.1 Meiotic role of nucleocytoplasmic traffic
2.2 Regulation of LINC complex by the polo kinase Cdc5

Meiotic checkpoint and nuclear organization ((A) Immnunofluorescence of meiotic chromosome spreads from S. cerevisiae stained with DAPI (chromatin), anti-Rad51 (unrepaired DSBs marker) and anti-tubulin (spindle marker) antibodies. In the wild type, all Rad51 foci have disappeared when MI and MII segregations take place. However, when the checkpoint is defective (ddc2 mutant), chromosome segregation occurs (elongated spindles) with unrepaired breaks (Rad51 foci) leading to inviable spores. (B) In vivo image of a meiotic prophase yeast nucleus with the telomeres of synapsed chromosomes (Chr) anchored in the nuclear envelope (NE) to drive their rapid movement throughout the nucleus.