Institute Biologia Funcional y Genomica

Salamanca, Spain

Institute Biologia Funcional y Genomica

Salamanca, Spain
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De Sena-Tomas C.,Institute Biologia Funcional y Genomica | Yu E.Y.,Cornell University | Calzada A.,CSIC - National Center for Biotechnology | Holloman W.K.,Cornell University | And 2 more authors.
Nucleic Acids Research | Year: 2015

The Ku heterodimer serves in the initial step in repairing DNA double-strand breaks by the non-homologous end-joining pathway. Besides this key function, Ku also plays a role in other cellular processes including telomere maintenance. Inactivation of Ku can lead to DNA repair defects and telomere aberrations. In model organisms where Ku has been studied, inactivation can lead to DNA repair defects and telomere aberrations. In general Ku deficient mutants are viable, but a notable exception to this is human where Ku has been found to be essential. Here we report that similar to the situation in human Ku is required for cell proliferation in the fungus Ustilago maydis. Using conditional strains for Ku expression, we found that cells arrest permanently in G2 phase when Ku expression is turned off. Arrest results from cell cycle checkpoint activation due to persistent signaling via the DNA damage response (DDR). Our results point to the telomeres as the most likely source of the DNA damage signal. Inactivation of the DDR makes the Ku complex dispensable for proliferation in this organism. Our findings suggest that in U. maydis, unprotected telomeres arising from Ku depletion are the source of the signal that activates the DDR leading to cell cycle arrest. © 2015 The Author(s).


Alzu A.,FIRC Institute of Molecular Oncology IFOM Foundation | Bermejo R.,FIRC Institute of Molecular Oncology IFOM Foundation | Bermejo R.,Institute Biologia Funcional y Genomica | Begnis M.,FIRC Institute of Molecular Oncology IFOM Foundation | And 13 more authors.
Cell | Year: 2012

Transcription hinders replication fork progression and stability. The ATR checkpoint and specialized DNA helicases assist DNA synthesis across transcription units to protect genome integrity. Combining genomic and genetic approaches together with the analysis of replication intermediates, we searched for factors coordinating replication with transcription. We show that the Sen1/Senataxin DNA/RNA helicase associates with forks, promoting their progression across RNA polymerase II (RNAPII)-transcribed genes. sen1 mutants accumulate aberrant DNA structures and DNA-RNA hybrids while forks clash head-on with RNAPII transcription units. These replication defects correlate with hyperrecombination and checkpoint activation in sen1 mutants. The Sen1 function at the forks is separable from its role in RNA processing. Our data, besides unmasking a key role for Senataxin in coordinating replication with transcription, provide a framework for understanding the pathological mechanisms caused by Senataxin deficiencies and leading to the severe neurodegenerative diseases ataxia with oculomotor apraxia type 2 and amyotrophic lateral sclerosis 4. © 2012 Elsevier Inc.


Santamaria R.,University of Salamanca | Theron R.,University of Salamanca | Quintales L.,University of Salamanca | Quintales L.,Institute Biologia Funcional y Genomica
Bioinformatics | Year: 2014

Motivation: Systems biology demands the use of several point of views to get a more comprehensive understanding of biological problems. This usually leads to take into account different data regarding the problem at hand, but it also has to do with using different perspectives of the same data. This multifaceted aspect of systems biology often requires the use of several tools, and it is often hard to get a seamless integration of all of them, which would help the analyst to have an interactive discourse with the data. Results: Focusing on expression profiling, BicOverlapper 2.0 visualizes the most relevant aspects of the analysis, including expression data, profiling analysis results and functional annotation. It also integrates several state-of-the-art numerical methods, such as differential expression analysis, gene set enrichment or biclustering. © 2014 The Author. Published by Oxford University Press. All rights reserved.


Castanheira S.,Institute Biologia Funcional y Genomica | Perez-Martin J.,Institute Biologia Funcional y Genomica
Plant Signaling and Behavior | Year: 2015

Many of the most important plant diseases are caused by fungal pathogens that form specialized cell structures to breach the leaf surface as well as to proliferate inside the plant. To initiate pathogenic development, the fungus responds to a set of inductive cues. Some of them are of extracellular nature (environmental signals) while others respond to intracellular conditions (developmental signals). These signals have to be integrated into a single response that has as a major outcome changes in the morphogenesis of the fungus. The cell cycle regulation is pivotal during these cellular differentiations, and we hypothesized that cell cycle regulation would be likely to provide control points for infection development by fungal pathogens. Although efforts have been done in various fungal systems, there is still limited information available regarding the relationship of these processes with the induction of the virulence programs. Hence, the role of fungal cell cycle regulators –which are wide conserved elements– as true virulence factors, has yet to be defined. Here we discuss the recent finding that the formation of the appressorium, a structure required for plant penetration, in the corn smut fungus Ustilago maydis seems to be incompatible with an active cell cycle and, therefore genetic circuits evolved in this fungus to arrest the cell cycle during the growth of this fungus on plant surface, before the appressorium-mediated penetration into the plant tissue. © 2015 Taylor & Francis Group, LLC.


Castanheira S.,Institute Biologia Funcional y Genomica | Mielnichuk N.,Institute Biologia Funcional y Genomica | Perez-Martin J.,Institute Biologia Funcional y Genomica
Development (Cambridge) | Year: 2014

Ustilago maydis is a plant pathogen that requires a specific structure called infective filament to penetrate the plant tissue. Although able to grow, this filament is cell cycle arrested on the plant surface. This cell cycle arrest is released once the filament penetrates the plant tissue. The reasons and mechanisms for this cell cycle arrest are unknown. Here, we have tried to address these questions. We reached three conclusions from our studies. First, the observed cell cycle arrest is the result of the cooperation of at least two distinct mechanisms: one involving the activation of the DNA damage response (DDR) cascade; and the other relying on the transcriptional downregulation of Hsl1, a kinase that modulates the G2/M transition. Second, a sustained cell cycle arrest during the infective filament step is necessary for the virulence in U. maydis, as a strain unable to arrest the cell cycle was severely impaired in its ability to infect corn plants. Third, production of the appressorium, a structure required for plant penetration, is incompatible with an active cell cycle. The inability to infect plants by strains defective in cell cycle arrest seems to be caused by their failure to induce the appressorium formation process. In summary, our findings uncover genetic circuits to arrest the cell cycle during the growth of this fungus on the plant surface, thus allowing the penetration into plant tissue. © 2014. Published by The Company of Biologists Ltd.


Perez-Martin J.,Institute Biologia Funcional y Genomica | Bardetti P.,Institute Biologia Funcional y Genomica | Castanheira S.,Institute Biologia Funcional y Genomica | de la Torre A.,Institute Biologia Funcional y Genomica | Tenorio-Gomez M.,Institute Biologia Funcional y Genomica
Seminars in Cell and Developmental Biology | Year: 2016

To initiate pathogenic development, pathogenic fungi respond to a set of inductive cues. Some of them are of an extracellular nature (environmental signals), while others are intracellular (developmental signals). These signals must be integrated into a single response whose major outcome is changes in the morphogenesis of the fungus. The regulation of the cell cycle is pivotal during these cellular differentiation steps; therefore, cell cycle regulation would likely provide control points for infectious development by fungal pathogens. Here, we provide clues to understanding how the control of the cell cycle is integrated with the morphogenesis program in pathogenic fungi, and we review current examples that support these connections. © 2016 Elsevier Ltd.


Fujimura T.,Institute Biologia Funcional y Genomica | Esteban R.,Institute Biologia Funcional y Genomica
Molecular Microbiology | Year: 2016

The 5′end of RNA conveys important information on self-identity. In mammalian cells, double-stranded RNA (dsRNA) with 5′di- or triphosphates generated during virus infection is recognized as foreign and elicits the host innate immune response. Here, we analyze the 5′ ends of the dsRNA genome of the yeast L-A virus. The positive strand has largely diphosphates with a minor amount of triphosphates, while the negative strand has only diphosphates. Although the virus can produce capped transcripts by cap snatching, neither strand carried a cap structure, suggesting that only non-capped transcripts serve as genomic RNA for encapsidation. We also found that the 5′ diphosphates of the positive but not the negative strand within the dsRNA genome are crucial for transcription in vitro. Furthermore, the presence of a cap structure in the dsRNA abrogated its template activity. Given that the 5′ diphosphates of the transcripts are also essential for cap acquisition and that host cytosolic RNAs (mRNA, rRNA, and tRNA) are uniformly devoid of 5′ pp-structures, the L-A virus takes advantage of its 5′ terminal diphosphates, using them as a self-identity tag to propagate in the host cytoplasm. © 2016 John Wiley & Sons Ltd


PubMed | Institute Biologia Funcional y Genomica
Type: Journal Article | Journal: Molecular microbiology | Year: 2016

The 5end of RNA conveys important information on self-identity. In mammalian cells, double-stranded RNA (dsRNA) with 5di- or triphosphates generated during virus infection is recognized as foreign and elicits the host innate immune response. Here, we analyze the 5 ends of the dsRNA genome of the yeast L-A virus. The positive strand has largely diphosphates with a minor amount of triphosphates, while the negative strand has only diphosphates. Although the virus can produce capped transcripts by cap snatching, neither strand carried a cap structure, suggesting that only non-capped transcripts serve as genomic RNA for encapsidation. We also found that the 5 diphosphates of the positive but not the negative strand within the dsRNA genome are crucial for transcription in vitro. Furthermore, the presence of a cap structure in the dsRNA abrogated its template activity. Given that the 5 diphosphates of the transcripts are also essential for cap acquisition and that host cytosolic RNAs (mRNA, rRNA, and tRNA) are uniformly devoid of 5 pp-structures, the L-A virus takes advantage of its 5 terminal diphosphates, using them as a self-identity tag to propagate in the host cytoplasm.


PubMed | Institute Biologia Funcional y Genomica
Type: | Journal: Methods in molecular biology (Clifton, N.J.) | Year: 2015

The synthesis of the septum is a critical step during cytokinesis in the fungal cell. Moreover, in Saccharomyces cerevisiae septum assembly depends mostly on the proper synthesis and deposition of chitin and, accordingly, on the timely regulation of chitin synthases. In this chapter, we will see how to follow chitin synthesis by two complementary approaches: monitoring chitin deposition in vivo at the septum by calcofluor staining and fluorescence microscopy, and measuring the chitin synthase activities responsible for this synthesis.


PubMed | University of Namur and Institute Biologia Funcional y Genomica
Type: | Journal: eLife | Year: 2016

In fission yeast, the ste11 gene encodes the master regulator initiating the switch from vegetative growth to gametogenesis. In a previous paper, we showed that the methylation of H3K4 and consequent promoter nucleosome deacetylation repress ste11 induction and cell differentiation (Materne et al., 2015) but the regulatory steps remain poorly understood. Here we report a genetic screen that highlighted H2B deubiquitylation and the RSC remodeling complex as activators of ste11 expression. Mechanistic analyses revealed more complex, opposite roles of H2Bubi at the promoter where it represses expression, and over the transcribed region where it sustains it. By promoting H3K4 methylation at the promoter, H2Bubi initiates the deacetylation process, which decreases chromatin remodeling by RSC. Upon induction, this process is reversed and efficient NDR (nucleosome depleted region) formation leads to high expression. Therefore, H2Bubi represses gametogenesis by opposing the recruitment of RSC at the promoter of the master regulator ste11 gene.

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