Chromosome Dynamics Group

Madrid, Spain

Chromosome Dynamics Group

Madrid, Spain
SEARCH FILTERS
Time filter
Source Type

Remeseiro S.,Chromosome Dynamics Group | Cuadrado A.,Chromosome Dynamics Group | Carretero M.,Chromosome Dynamics Group | Martnez P.,Telomeres and Telomerase Group | And 5 more authors.
EMBO Journal | Year: 2012

Cohesin is a protein complex originally identified for its role in sister chromatid cohesion, although increasing evidence portrays it also as a major organizer of interphase chromatin. Vertebrate cohesin consists of Smc1, Smc3, Rad21/Scc1 and either stromal antigen 1 (SA1) or SA2. To explore the functional specificity of these two versions of cohesin and their relevance for embryonic development and cancer, we generated a mouse model deficient for SA1. Complete ablation of SA1 results in embryonic lethality, while heterozygous animals have shorter lifespan and earlier onset of tumourigenesis. SA1-null mouse embryonic fibroblasts show decreased proliferation and increased aneuploidy as a result of chromosome segregation defects. These defects are not caused by impaired centromeric cohesion, which depends on cohesin-SA2. Instead, they arise from defective telomere replication, which requires cohesion mediated specifically by cohesin-SA1. We propose a novel mechanism for aneuploidy generation that involves impaired telomere replication upon loss of cohesin-SA1, with clear implications in tumourigenesis. © 2012 European Molecular Biology Organization | All Rights Reserved.


Cuadrado A.,Chromosome Dynamics Group | Remeseiro S.,Chromosome Dynamics Group | Remeseiro S.,European Molecular Biology Laboratory | Grana O.,Bioinformatics Unit | And 2 more authors.
Nucleic Acids Research | Year: 2015

Cohesin, which in somatic vertebrate cells consists of SMC1, SMC3, RAD21 and either SA1 or SA2, mediates higher-order chromatin organization. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these show reduced overlap with CCCTC-binding factor (CTCF) and are enriched at the regulatory regions of tissue-specific genes. Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1. Analyses of chromatin contacts at the Protocadherin (Pcdh) and Regenerating islet-derived (Reg) gene clusters, mostly expressed in brain and pancreas, respectively, revealed remarkable differences that correlate with the presence of cohesin. We could not detect significant changes in the chromatin contacts at the Pcdh locus when comparing brains from wild-type and SA1 null embryos. In contrast, reduced dosage of SA1 altered the architecture of the Reg locus and decreased the expression of Reg genes in the pancreas of SA1 heterozygous mice. Given the role of Reg proteins in inflammation, such reduction may contribute to the increased incidence of pancreatic cancer observed in these animals. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.


Rivera T.,Chromosome Dynamics Group | Rivera T.,Salk Institute for Biological Studies | Ghenoiu C.,Rockefeller University | Rodriguez-Corsino M.,Chromosome Dynamics Group | And 3 more authors.
EMBO Journal | Year: 2012

Shugoshins (Sgo) are conserved proteins that act as protectors of centromeric cohesion and as sensors of tension for the machinery that eliminates improper kinetochore-microtubule attachments. Most vertebrates contain two Sgo proteins, but their specific functions are not always clear. Xenopus laevis Sgo1, XSgo1, protects centromeric cohesin from the prophase dissociation pathway. Here, we report the identification of XSgo2 and show that it does not regulate cohesion. Instead, we find that it participates in bipolar spindle assembly. Both Sgo proteins interact physically with the Chromosomal Passenger Complex (CPC) containing Aurora B, a key regulator of mitosis, but the functional consequences of such interaction are distinct. XSgo1 is required for proper localization of the CPC while XSgo2 positively contributes to its activation and the subsequent phosphorylation of at least one key substrate for bipolar spindle assembly, the microtubule depolymerizing kinesin MCAK (Mitotic Centromere-Associated Kinesin). Thus, the two Xenopus Sgo proteins have non-overlapping functions in chromosome segregation. Our results further suggest that this functional specificity could rely on the association of XSgo1 and XSgo2 with different regulatory subunits of the PP2A complex. © 2012 European Molecular Biology Organization.


Carretero M.,Chromosome Dynamics Group | Remeseiro S.,Chromosome Dynamics Group | Losada A.,Chromosome Dynamics Group
Current Opinion in Cell Biology | Year: 2010

Cohesin was originally identified as a mediator of sister chromatid cohesion both in mitosis and meiosis. Emerging evidences suggest that it also participates in the organization of interphase chromatin. The ring-shaped complex regulates gene expression by constraining chromatin topology in concert with factors such as the insulator CTCF, at least in certain loci. The global relevance of this function of cohesin remains to be assessed, but its contribution to the pathology of the Cornelia de Lange syndrome seems evident. Our current knowledge of the molecular mechanisms underlying cohesin behavior should now be considered from the perspective of its novel functions, which promise to be as relevant for cell viability as cohesion. © 2010 Elsevier Ltd.


Remeseiro S.,Chromosome Dynamics Group | Cuadrado A.,Chromosome Dynamics Group | Gomez-Lapez G.,Bioinformatics Unit | Pisano D.G.,Bioinformatics Unit | Losada A.,Chromosome Dynamics Group
EMBO Journal | Year: 2012

Vertebrates have two cohesin complexes that consist of Smc1, Smc3, Rad21/Scc1 and either SA1 or SA2, but their functional specificity is unclear. Mouse embryos lacking SA1 show developmental delay and die before birth. Comparison of the genome-wide distribution of cohesin in wild-type and SA1-null cells reveals that SA1 is largely responsible for cohesin accumulation at promoters and at sites bound by the insulator protein CTCF. As a consequence, ablation of SA1 alters transcription of genes involved in biological processes related to Cornelia de Lange syndrome (CdLS), a genetic disorder linked to dysfunction of cohesin. We show that the presence of cohesin-SA1 at the promoter of myc and of protocadherin genes positively regulates their expression, a task that cannot be assumed by cohesin-SA2. Lack of SA1 also alters cohesin-binding pattern along some gene clusters and leads to dysregulation of genes within. We hypothesize that impaired cohesin-SA1 function in gene expression underlies the molecular aetiology of CdLS. © 2012 European Molecular Biology Organization | All Rights Reserved.


Remeseiro S.,Chromosome Dynamics Group | Losada A.,Chromosome Dynamics Group
Current Opinion in Cell Biology | Year: 2013

Cohesin is a four subunit complex, conserved from yeast to man, with the ability to hold together two DNA segments within its ring-shaped structure. When the two segments belong to sister chromatids, cohesin is mediating cohesion, which is essential for chromosome segregation in mitosis and meiosis and for homologous DNA repair. When the two DNA segments are in the same chromatid, a loop is formed. These chromatin loops are emerging as a mechanism for controlling the communication between enhancers and promoters and thereby regulate gene expression. They also facilitate DNA replication and recombination. Given all its essential functions, it is not surprising that mutations in cohesin and its interacting factors have been associated to cancer and developmental syndromes known as cohesinopathies. © 2012 Elsevier Ltd.


Losada A.,Chromosome Dynamics Group
Nature Reviews Cancer | Year: 2014

Cohesin is an evolutionarily conserved, four-subunit complex that entraps DNA fibres within its ring-shaped structure. It was originally identified and named for its role in mediating sister chromatid cohesion, which is essential for chromosome segregation and DNA repair. Increasing evidence indicates that cohesin participates in other processes that involve DNA looping, most importantly, transcriptional regulation. Mutations in genes encoding cohesin subunits and other regulators of the complex have recently been identified in several types of tumours. Whether aneuploidy that results from chromosome missegregation is the major contribution of cohesin mutations to cancer progression is under debate. © 2014 Macmillan Publishers Limited.


Remeseiro S.,Chromosome Dynamics Group
Current opinion in cell biology | Year: 2013

Cohesin is a four subunit complex, conserved from yeast to man, with the ability to hold together two DNA segments within its ring-shaped structure. When the two segments belong to sister chromatids, cohesin is mediating cohesion, which is essential for chromosome segregation in mitosis and meiosis and for homologous DNA repair. When the two DNA segments are in the same chromatid, a loop is formed. These chromatin loops are emerging as a mechanism for controlling the communication between enhancers and promoters and thereby regulate gene expression. They also facilitate DNA replication and recombination. Given all its essential functions, it is not surprising that mutations in cohesin and its interacting factors have been associated to cancer and developmental syndromes known as cohesinopathies. Copyright © 2012 Elsevier Ltd. All rights reserved.


Remeseiro S.,Chromosome Dynamics Group | Cuadrado A.,Chromosome Dynamics Group | Losada A.,Chromosome Dynamics Group
Development (Cambridge) | Year: 2013

Cohesin is a ring-shaped complex, conserved from yeast to human, that was named for its ability to mediate sister chromatid cohesion. This function is essential for chromosome segregation in both mitosis and meiosis, and also for DNA repair. In addition, more recent studies have shown that cohesin influences gene expression during development through mechanisms that likely involve DNA looping and interactions with several transcriptional regulators. Here, we provide an overview of how cohesin functions, highlighting its role both in development and in disease. © 2013. Published by The Company of Biologists Ltd.


Carretero M.,Chromosome Dynamics Group | Ruiz-Torres M.,Chromosome Dynamics Group | Rodriguez-Corsino M.,Chromosome Dynamics Group | Barthelemy I.,Chromosome Dynamics Group | Losada A.,Chromosome Dynamics Group
EMBO Journal | Year: 2013

Cohesin mediates sister chromatid cohesion and contributes to the organization of interphase chromatin through DNA looping. In vertebrate somatic cells, cohesin consists of Smc1, Smc3, Rad21, and either SA1 or SA2. Three additional factors Pds5, Wapl, and Sororin bind to cohesin and modulate its dynamic association with chromatin. There are two Pds5 proteins in vertebrates, Pds5A and Pds5B, but their functional specificity remains unclear. Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin. While both proteins contribute to telomere and arm cohesion, Pds5B is specifically required for centromeric cohesion. Furthermore, reduced accumulation of Aurora B at the inner centromere region in cells lacking Pds5B impairs its error correction function, promoting chromosome mis-segregation and aneuploidy. Our work supports a model in which the composition and function of cohesin complexes differs between different chromosomal regions. © 2013 European Molecular Biology Organization.

Loading Chromosome Dynamics Group collaborators
Loading Chromosome Dynamics Group collaborators