Pedro San-Segundo

Meiotic Chromosome Dynamics
http://ibfg.es/en/pedro-san-segundo-en

Research interest

Meiosis is the specialized cell division that produces haploid gametes from diploid parental cells (gametogenesis). 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. Meiotic 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.

During meiosis, the processes of pairing, synapsis and recombination are crucial to establish physical connections between homologous chromosomes that orchestrate their segregation during the first meiotic division. Given the importance of these events, meiotic cells have developed 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 defects in recombination and/or chromosome synapsis, thus preventing aberrant chromosome segregation and the formation of aneuploid gametes.

The budding yeast Saccharomyces cerevisiae possesses robust meiotic quality control systems. Given the evolutionary conservation of checkpoint pathways and the proteins involved, as well as the ample array of research tools available, this is an excellent model system to make progress in the understanding of the molecular basis of fertility problems. We are focused on different aspects of the molecular mechanisms underlying the meiotic checkpoint response in yeast, from the detection of the errors to the signaling pathways and the cell cycle arrest outcome.

Publications

  • Refolio, E., Cavero, S., Marcon, E., Freire. R. and San-Segundo, P.A.. (2011) The Ddc2/ATRIP checkpoint protein monitors meiotic recombination intermediates. Journal of Cell Science 124: 2488-2500

  • Farmer, S., San-Segundo, P.A. and Aragón, L. (2011). The Smc5-Smc6 complex is required to remove chromosome junctions in meiosis. PLoS One 6: e20948

  • Acosta, I. Ontoso, D. and San-Segundo, P.A. (2011). The Budding Yeast Polo-Like Kinase Cdc5 Regulates the Ndt80 Branch of the Meiotic Recombination Checkpoint Pathway Molecular Biology of the Cell 22: 3478-3490

  • Ontoso D, Acosta I, van Leeuwen F, Freire R, San-Segundo P (2013) Dot1-dependent histone H3K79 methylation promotes activation of the Mek1 meiotic checkpoint effector kinase by regulating the Hop1 adaptor PLOS Genetics 9: e1003262

  • Ontoso, D., Kauppi, L., Keeney, S. and San-Segundo, P. (2014) Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in mouse spermatocytes Chromosoma 123: 147-164

  • Vlaming H, van Welsem,T, de Graaf, EL, Ontoso, D, Altelaar, AM, San-Segundo, PA, Heck, AJ, van Leeuwen F. (2014) Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo. EMBO Rep. 15:1077-1084

  • Herruzo E., Ontoso D., González-Arranz S., Cavero S., Lechuga A. and San-Segundo P. (2016) The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects. Nucleic Acids Res. 44: 7722-7741

  • Cavero S., Herruzo E., Ontoso D. and San-Segundo P. (2016) Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae Microbial Cell 2016. 3(12): 475-489

Active Grants

  • Checkpoint control of meiotic chromosome dynamics during gametogenesis MINECO. BFU2015-65417-R 2016-2018 130.000 Euro IP: Pedro San-Segundo

  • Coordination between cell cycle and chromosome dynamics during meiosis: implications in fertility Junta de Castilla y León. CSI084U16 2016-2018 40.000 Euro Coordinator: Sergio Moreno

  • Group members

    • Pedro San-Segundo (Principal Investigator)
    • Sara González-Arranz (Predoc)
    • Esther Herruzo (Predoc)
    • David Núñez Nepomuceno (Undergraduate student)