Cristina Martín Castellanos

Control of the initiation of meiotic recombination

Meiosis is a specialized cell division essential in sexually reproducing organisms. A key feature of meiosis is recombination between homologous (maternal and paternal) chromosomes that, in addition to generate genetic diversity, facilitates accurate chromosome segregation. Defects in chromosome segregation during meiosis cause miscarriages, infertility and genetic diseases, and reveal the important to understand the meiotic recombination process.

We are interested in how this particular recombination is regulated, what determines in which chromosome regions takes place and how the activity of the topoisomerase-like protein that initiates the process is controlled. To this aim we are using the fission yeast Schizosaccharomyces pombe, since this organism is a proven model system for different eukaryotic conserved processes.

In particular our aims are:

  • To understand how the conserved protein Rec12 (Spo11) is regulated.
    Rec12 generates the double-strand breaks (DSB) that initiate recombination, and its activity needs to be highly controlled to avoid unwanted DNA damage that can be deleterious to the cell. Although Rec12 is essential for DSB formation it does not function alone, and requires a plethora of accessory proteins of unclear function. Recently we have described a functional interaction between two of these proteins (Rec24 and Rec7) as part of the recombination-initiation complex (Bonfils et al. 2011). We would like to understand the role of these proteins in the complex and to study a possible role in the loading and/or activation of Rec12 onto the recombination hotspots.
  • To understand how Linear Elements (LinEs) control recombination.
    LinEs are dynamic chromosome structures similar to the synaptonemal complex of other eukaryotes, and are required for meiotic recombination (Davis et al. 2008). They serve as platforms where Rec12-accessory proteins are loaded.
    Recently in collaboration with the group of Dr. Gerald R. Smith (Fred Hutchinson Cancer Research Center, Seattle) we have shown that LinE-components determine both where in the genome DSB-sites are placed, and the efficiency of the breakage (Fowler et al., 2013).


 

Group members
Cristina Martín Castellanos Research Scientist (CSIC)
Luisa F. Bustamante Jaramillo PhD Student
Luis Antonio de Castro Anta Technician
Recent publications
Ma L, Fowler KR, Martín-Castellanos C, Smith GR (2017).
Functional organization of protein determinants of meiotic DNA break hotspots
Scientific Reports 7:1393
Martín-Castellanos C, Fowler KR and Smith GR (2013)
Making chromosomes hot for breakage.
Cell Cycle 12: 1327-1328
Fowler KR, Gutiérrez-Velasco S, Martín-Castellanos C and Smith GR (2013)
Protein determinants of meiotic DNA break hotspots
Mol. Cell 49: 983-996
Bonfils S, Rozalén AE, Smith GR, Moreno S and Martín-Castellanos C (2011)
Functional interactions of Rec24, the fission yeast ortholog of mouse Mei4, with the meiotic recombination-initiation complex
J. Cell Sci. 124: 1328-1338
Davis L, Rozalén AE, Moreno S, Smith G and Martín-Castellanos C (2008)
Rec25 and Rec27, novel linear-element components, link cohesin to meiotic DNA breakage and recombination
Curr. Biol. 18: 849-854
Research grants
MINECO (BFU2013-45182-P)
MINECO: Biología Funcional de la Red Meiótica, MEIONet (Acciones de Dinamización «Redes de Excelencia ») (BFU2015-71786-REDT).
Junta de Castilla y León: CSI084U16. Unidad de Investigación Consolidada de Castilla y León: UIC 028.
Links of interest
MeioNet
Meiotically upregulated genes (mug)
Master en Biología Celular y Molecular