Control of sister chromatid cohesion/separation is critical to ensure faithful chromosome segregation during mitosis and meiosis. Failures in this mechanism during mitosis often lead to aneuploidy and chromosome instability, a major cause of cancer, while failures during meiosis promote miscarriage, birth defects, and infertility in humans. A key protagonist in this control is the cohesin complex, which are composed essentially by four subunits, two of them, called Smc1 and Smc3 (Structural maintenance of chromosomes), are members of a highly conserved protein family also found in prokaryotes and are implicated in various functions related to DNA dynamics, dose compensation, chromosome condensation, recombination, etc. The other two subunits are specific to eukaryotes and, depending on the organism, are termed Scc1/Rad21 or Scc3/STAG, the former mainly for yeast and the latter in higher eukaryotes. In addition to their function in chromatid cohesion during chromosome segregation, our previous results and recent evidences implicate the cohesins in completely different processes, including the regulation of gene expression, DNA repair, and development, suggesting that cohesin functions are more than the glue of chromosomes.
Using the molecular tools previously generated in our laboratory, now we are focused on the study of the composition and role of different cohesin complexes and the cohesin-interacting proteins shugoshins during the mammalian meiotic cell cycle.
Casey AE, Daish TJ, Barbero JL, Grützner F. . Differential cohesin loading marks paired and unpaired regions of platypus sex chromosomes at prophase I. Sci. Rep. 7(1):4217. doi: 10.1038/s41598-017-04560-5.
MIguel-A Brieño-Enriquez, Steffanie L. Moak, Melissa Toledo, Joshua J. Filter, Stephen Gray, José L. Barbero, Paula E. Cohen and J. Kim Holloway . Cohesin removal along the chromosome arms during the first meiotic division depends on a NEK1-PP1g-WAPL axis in the mouse. Cell Reports 17,977-986.
Gómez-H L, Felipe-Medina N, Sánchez-Martín M, Davies OR, Ramos I, García-Tuñón I, de Rooij DG, Dereli I, Tóth A, Barbero JL, Benavente R, Llano E, Pendas AM. . C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility.. Nat Commun. 2016 Oct 31;7:13298. doi: 10.1038/ncomms13298.
Sánchez L, Chaouiya C . Primary sex determination of placental mammals: a modelling study uncovers dynamical developmental constraints in the formation of Sertoli and granulosa cells. BMC Systems Biology 10:37.
Gómez R, Felipe-Medina N, Ruiz-Torres M, Berenguer I, Viera A, Pérez S, Barbero JL, Llano E, Fukuda T, Alsheimer M, Pendás AM, Losada A, Suja JA. . Sororin loads to the synaptonemal complex central region independently of meiotic cohesin complexes. EMBO Rep. 7: 695-707
Ruiz MF, Alvarez M, Eirín-López JM, Sarno F, Kremer L, Barbero JL, Sánchez L . An Unusual Role for doublesex in Sex Determination in the Dipteran Sciara. Genetics.200(4):1181-1199
Eirin-López JM, Sánchez L . The comparative study of five sex-determining proteins across insects unveils high rates of evolution at basal components of the sex determination cascade. Dev. Genes Evol. 225:23-30.
Caburet S., Arboleda VA, Llano E., Overbeek PA, Barbero JL, Oka K., Harrison W., Vaiman D., Ben-Neriah Z., Garcia-Tuñon I., Fellous M., Pendás AM, Veitia RA and Vilain E . Mutant Cohesin in Premature Ovarian Failure. New England J. Med. 370:943-949
Barbero, JL . Molecular Genetics of Cohesinopathies. In: eLS. John Wiley&Sons Ltd, Chichester. doi: 10.1002/9780470015902.a0025309
Sánchez L . Sex determining mechanisms in insects based on imprinting and elimination of chromosomes. Sexual development 8: 83-103
.CHROMOSOME SEGREGATION CONTROL IN MAMMALIAN MEIOSIS: ROLE OF COHESINS AND SHUGOSHINS. (BFU2006-04406/BMC).
.TRANSLATIONAL INDIVIDUALIZED MEDICINE IN INFLAMATION AND CANCER. PROGRAM MITIC-CM. COMUNIDAD DE MADRID. P-BIO-0189-2006.
CHROMOSOME SEGREGATION CONTROL IN MAMMALIAN MEIOSIS: ROEL OF COHESIN-REGULATORS PDS5, SORORIN AND SHUGOSHINS.(BFU2009-08975/BMC).
. BIOLOGICAL FUNCTION OF ESCO1 AND ESCO2 ACETYLTRANSFERASES IN THE CHROMOSOME SEGREGATION DURING MAMMALIAN MEIOSIS. PIE.CSIC. 201120E020
. MOLECULAR BASIS OF ANEUPLOIDY IN CANCER:CHROMOSOME SEGREGATION CONTROL AND CHROMOSOME STABILITY. FUNDACIÓN DE INVESTIGACIÓN MÉDICA MUTUA MADRILEÑA. AP 98712012 (2012-2014).
.FUNCTIONAL ANALYSIS OF THE COHESIN NETWORK IN MAMMALS.(BFU2014-59307-R). (01/01/2015-31/12/2017).