Suchergebnisse

Este trabajo de investigación busca formular una política comprehensiva de inversión extranjera para América Latina y Colombia en la producción de "commodities" como petróleo, gas, oro, plata, metales industriales y otros menos conocidos pero valiosos, esto es minerales "exóticos" como el coltan (es una mezcla de los minerales columbita y tantalita) cuyos elementos son considerados "críticos" para industrias altamente tecnológicas por ejemplo defensa, aeroespacial y telecomunicaciones, debido a sus particulares propiedades físicas y químicas. Este trabajo estudia los patrones de flujos de IED hacia Colombia en años recientes y los resultados de las medidas de promoción de inversión adoptadas por el Gobierno colombiano especialmente en el sector minero. Se identifica una importante tendencia de convergencia entre los gobiernos de Corea del Sur y Colombia en estas áreas, que puede ser explotada para ventaja mutua, en un marco de libre comercio. Sin embargo, la política de convergencia requiere ser probada de manera empírica en la implementación de política. ; This research paper aims to formulate a comprehensive foreign investment policy towards Latin America and Colombia in commodities production like oil, gas, gold, silver, industrial metals, and other less known but valuable minerals, such as 'exotic' minerals like coltan (columbium or niobium and tantalum) whose elements are considered 'critical' for hi-tech industries i.e. defence, aerospace and communications due to their particular physical and chemical properties. Particularly, the paper studies the parttern of FDI inflows to Colombia in recent years and the results of the investment promotion measures taken by the Colombian government especially in the mining sector. An important policy convergence is found between Colombia and South Korea in those areas, that can be exploited to mutual advantage in a Free Trade Agreement framework being concluded between the two countries. However, the policy convergence still needs to be tested into policy action.

During transcription, the nascent pre-mRNA undergoes a series of processing steps before being exported to the cytoplasm. The 3′-end processing machinery involves different proteins, this function being crucial to cell growth and viability in eukaryotes. Here, we found that the rna14-1, rna15-1, and hrp1-5 alleles of the cleavage factor I (CFI) cause sensitivity to UV-light in the absence of global genome repair in Saccharomyces cerevisiae. Unexpectedly, CFI mutants were proficient in UV-lesion repair in a transcribed gene. DNA damage checkpoint activation and RNA polymerase II (RNAPII) degradation in response to UV were delayed in CFI-deficient cells, indicating that CFI participates in the DNA damage response (DDR). This is further sustained by the synthetic growth defects observed between rna14-1 and mutants of different repair pathways. Additionally, we found that rna14-1 suffers severe replication progression defects and that a functional G1/S checkpoint becomes essential in avoiding genetic instability in those cells. Thus, CFI function is required to maintain genome integrity and to prevent replication hindrance. These findings reveal a new function for CFI in the DDR and underscore the importance of coordinating transcription termination with replication in the maintenance of genomic stability. ; This research was funded by grants from the Spanish Ministry of Economy and Competitiveness (Consolider Ingenio 2010 CSD2007-0015 and BFU2010- 16372; www.mineco.gob.es), Junta de Andalucía (CVI-4567; www.juntadeandalucia.es) and the European Union (FEDER). ; Peer reviewed

This is an open-access article distributed under the terms of the Creative Commons Attribution License. ; DNA double-strand break (DSB) repair occurring in repeated DNA sequences often leads to the generation of chromosomal rearrangements. Homologous recombination normally ensures a faithful repair of DSBs through a mechanism that transfers the genetic information of an intact donor template to the broken molecule. When only one DSB end shares homology to the donor template, conventional gene conversion fails to occur and repair can be channeled to a recombinationdependent replication pathway termed break-induced replication (BIR), which is prone to produce chromosome nonreciprocal translocations (NRTs), a classical feature of numerous human cancers. Using a newly designed substrate for the analysis of DSB–induced chromosomal translocations, we show that Mus81 and Yen1 structure-selective endonucleases (SSEs) promote BIR, thus causing NRTs. We propose that Mus81 and Yen1 are recruited at the strand invasion intermediate to allow the establishment of a replication fork, which is required to complete BIR. Replication template switching during BIR, a feature of this pathway, engenders complex chromosomal rearrangements when using repeated DNA sequences dispersed over the genome. We demonstrate here that Mus81 and Yen1, together with Slx4, also promote template switching during BIR. Altogether, our study provides evidence for a role of SSEs at multiple steps during BIR, thus participating in the destabilization of the genome by generating complex chromosomal rearrangements. ; This work was funded by grants from the Spanish Ministry of Science and Innovation (BFU2006-05260, BFU2010-16370, and Consolider Ingenio 2010 CSD2007-015), Junta de Andalucía (BIO-102 and CVI-4567), and the European Union (FEDER). BP was supported by fellowships from Fondation Recherche Médicale (SPE20061209019) and EMBO (1003-2006) and a contract of the Juan de la Cierva Program of the Spanish Ministry of Science and Innovation (JCI 2009-04101). ; Peer reviewed

Este artículo evalúa críticamente el rol de las instituciones internacionales, bajo la visión de los neo-gramscianos y los institucionalistas liberales. Los neo-gramscianos argumentan que el propósito de las instituciones internacionales es mantener el poder hegemónico. Y para lograr este propósito, el sistema capitalista se ha extendido a través de las políticas de libre comercio de la OMC y condicionesen los préstamos del FMI y del Banco Mundial. Por su parte, los institucionalistasliberales sostienen que las instituciones internacionales han permitido la cooperación y facilitado la consecución de objetivos comunes, disminuyendo lainfluencia del poder hegemónico.

It has been long known that some regions of the genome are more susceptible to damage and mutagenicity than others. Recent advances have determined a critical role of chromatin both in the incidence of damage and in its repair. Thus, chromatin arises as a guardian of the stability of the genome, which is altered in cancer cells. In this review, we focus into the mechanisms by which chromatin influences the occurrence and repair of the most cytotoxic DNA lesions, double-strand breaks, in particular at actively transcribed chromatin or related to DNA replication. ; Research in AA's lab is funded by the European Research Council, the Spanish Ministry of Economy and Competitiveness, Junta de Andalucía and the European Union (FEDER).

R loops are nucleic acid structures comprising an DNA–RNA hybrid and a displaced single-stranded DNA. These structures may occur transiently during transcription, playing essential biological functions. However, persistent R loops may become pathological as they are important drivers of genome instability and have been associated with human diseases. The mitochondrial degradosome is a functionally conserved complex from bacteria to human mitochondria. It is composed of the ATP-dependent RNA and DNA helicase SUV3 and the PNPase ribonuclease, playing a central role in mitochondrial RNA surveillance and degradation. Here we describe a new role for the mitochondrial degradosome in preventing the accumulation of pathological R loops in the mitochondrial DNA, in addition to preventing dsRNA accumulation. Our data indicate that, similar to the molecular mechanisms acting in the nucleus, RNA surveillance mechanisms in the mitochondria are crucial to maintain its genome integrity by counteracting pathological R-loop accumulation. ; Research was funded by the European Research Council (Grant ERC2014 AdG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (Grants BFU2013-42918-P and BFU2016-75058-P), and the European Union (Fondo Europeo de Desarrollo Regional). S.S. was awarded a Juan de la Cierva–Incorporación grant from the Spanish Ministry of Economy, Industry, and Competitiveness during part of this study. ; Peer reviewed

En un contexto pandémico cargado de crisis socioeconómica, el campo de la odontología también ha tenido desafíos para prestar sus servicios, ya que atender a los pacientes implica altos riesgos de infección en los ambientes odontológicos; sin embargo, los compromisos con la sociedad les han conllevado a reconfigurar sus acciones, en concordancia con las necesidades del mercado. En ese marco, la presente investigación tuvo como objetivo determinar las estrategias de marketing implementadas por los centros especializados de odontología en el cantón de Ambato (Ecuador), para afrontar la crisis económica generada por el COVID-19. Para ello, se indagó sobre el marketing estratégico consultando las posturas de Lambín (2009), Kotler y Armstrong (2007) y Munuera y Rodríguez (2012), entre otros. Metodológicamente se acudió a un tipo de investigación aplicada-descriptiva, con un diseño de campo-transeccional. La población estuvo conformada por todos los centros especializados de odontología activos y con infraestructura física en el cantón de Ambato, siendo los agentes informantes los odontólogos que prestan sus servicios en los mencionados centros. La técnica para la recolección de datos fue la encuesta, mediante un cuestionario estructurado con escala likert, validado su contenido por cinco (5) expertos en mercadeo y se midió la confiabilidad mediante el coeficiente Alfa de Cronbach, el cual arrojó 0.99. Los resultados evidencian una tendencia positiva en la implementación de estrategias de marketing orientadas hacia la diversificación, el crecimiento y la competitividad. Se concluye que, los centros especializados de odontología desarrollan estrategias de marketing para afrontar el entorno turbulento y poder desenvolverse en términos competitivos, acorde a las necesidades odontológicas de la sociedad local.

DNA lesions interfere with cellular processes such as transcription and replication and need to be adequately resolved to warrant genome integrity. Beyond their primary role in molecule transport, nuclear pore complexes (NPCs) function in other processes such as transcription, nuclear organization and DNA double strand break (DSB) repair. Here we found that the removal of UV-induced DNA lesions by nucleotide excision repair (NER) is compromised in the absence of the Nup84 nuclear pore component. Importantly, nup84Δ cells show an exacerbated sensitivity to UV in early S phase and delayed replication fork progression, suggesting that unrepaired spontaneous DNA lesions persist during S phase. In addition, nup84Δ cells are defective in the repair of replication-born DSBs by sister chromatid recombination (SCR) and rely on post-replicative repair functions for normal proliferation, indicating dysfunctions in the cellular pathways that enable replication on damaged DNA templates. Altogether, our data reveal a central role of the NPC in the DNA damage response to facilitate replication progression through damaged DNA templates by promoting efficient NER and SCR and preventing chromosomal rearrangements. ; European Research Council [ERC2014 AdG669898 TARLOOP to A.A.]; Spanish Ministry of Economy and Competitiveness [BFU2016-75058-P to A.A.]; Junta de Andalucía [PA12-BIO1238 to A.A.]; European Union Regional Funds (FEDER). Funding for open access charge: European Research Council [ERC2014 AdG669898 TARLOOP]; Spanish Ministry of Economy and Competitiveness [BFU2016-75058-P].

Nucleotide Excision Repair (NER) is a pathway that removes lesions distorting the DNA helix. The molecular basis of the rare diseases Xeroderma pigmentosum (XP) and Cockayne Syndrome (CS) are explained based on the defects happening in 2 NER branches: Global-Genome Repair and Transcription-Coupled Repair, respectively. Nevertheless, both afflictions sporadically occur together, giving rise to XP/CS; however, the molecular basis of XP/CS is not understood very well. Many efforts have been made to clarify why mutations in only 4 NER genes, namely XPB, XPD, XPF and XPG, are the basis of this disease. Effort has also been made to unravel why mutations within these genes lead to XP, XP/CS, or other pathologies. We have recently contributed to the disclosure of this puzzle by characterizing Rad3/XPD mutations in Saccharomyces cerevisiae and human cells. Based on our, and others', observations, we propose a model compatible with all XP/CS cases and the current bibliography. ; Research in AA's lab is funded by grants from the Spanish Ministry of Economy and Competitiveness, the Junta de Andalucıa and the European Union (FEDER).

This is an open-access article distributed under the terms of the Creative Commons Attribution License. ; THO is a conserved eukaryotic complex involved in mRNP biogenesis and RNA export that plays an important role in preventing transcription- and RNA-mediated genome instability in mitosis and meiosis. In mammals THO is essential for embryogenesis, which limits our capacity to analyze the physiological relevance of THO during development and in adult organisms. Using Caenorhabditis elegans as a model system we show that the THO complex is essential for mitotic genome integrity and the developmentally regulated mitotic cell cycles occurring during late postembryonic stages. ; This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU2010-16372 and Consolider Ingenio 2010 CSD2007-0015), the European Union (FEDER) and the Junta de Andalucía (CVI4567). MCP was the recipient of a predoctoral training fellowship from the Spanish National Institute of Health Carlos III. ; Peer reviewed

DNA double-strand breaks (DSBs) are harmful lesions that arise mainly during replication. The choice of the sister chromatid as the preferential repair template is critical for genome integrity, but the mechanisms that guarantee this choice are unknown. Here we identify new genes with a specific role in assuring the sister chromatid as the preferred repair template. Physical analyses of sister chromatid recombination (SCR) in 28 selected mutants that increase Rad52 foci and inter-homolog recombination uncovered 8 new genes required for SCR. These include the SUMO/Ub-SUMO protease Wss1, the stress-response proteins Bud27 and Pdr10, the ADA histone acetyl-transferase complex proteins Ahc1 and Ada2, as well as the Hst3 and Hst4 histone deacetylase and the Rtt109 histone acetyl-transferase genes, whose target is histone H3 Lysine 56 (H3K56). Importantly, we use mutations in H3K56 residue to A, R, and Q to reveal that H3K56 acetylation/deacetylation is critical to promote SCR as the major repair mechanism for replication-born DSBs. The same phenotype is observed for a particular class of rad52 alleles, represented by rad52-C180A, with a DSB repair defect but a spontaneous hyper-recombination phenotype. We propose that specific Rad52 residues, as well as the histone H3 acetylation/deacetylation state of chromatin and other specific factors, play an important role in identifying the sister as the choice template for the repair of replication-born DSBs. Our work demonstrates the existence of specific functions to guarantee SCR as the main repair event for replication-born DSBs that can occur by two pathways, one Rad51-dependent and the other Pol32-dependent. A dysfunction can lead to genome instability as manifested by high levels of homolog recombination and DSB accumulation. ; Research was funded by grants from the Spanish Ministry of Science and Innovation (BFU2010-16372 and Consolider Ingenio 2010 CSD2007-0015), the Junta de Andalucía (BIO-102 and P09/CVI4567), and the European Union (FEDER) to AA and from the National Institutes of Health (GM50237 and GM67055) to RR. ; Peer reviewed

The eukaryotic TFIIH complex is involved in Nucleotide Excision Repair and transcription initiation. We analyzed three yeast mutations of the Rad3/XPD helicase of TFIIH known as rem (recombination and mutation phenotypes). We found that, in these mutants, incomplete NER reactions lead to replication fork breaking and the subsequent engagement of the homologous recombination machinery to restore them. Nevertheless, the penetrance varies among mutants, giving rise to a phenotype gradient. Interestingly, the mutations analyzed reside at the ATP-binding groove of Rad3 and in vivo experiments reveal a gain of DNA affinity upon damage of the mutant Rad3 proteins. Since mutations at the ATP-binding groove of XPD in humans are present in the Xeroderma pigmentosum-Cockayne Syndrome (XP-CS), we recreated rem mutations in human cells, and found that these are XP-CS-like. We propose that the balance between the loss of helicase activity and the gain of DNA affinity controls the capacity of TFIIH to open DNA during NER, and its persistence at both DNA lesions and promoters. This conditions NER efficiency and transcription resumption after damage, which in human cells would explain the XP-CS phenotype, opening new perspectives to understand the molecular basis of the role of XPD in human disease. ; Research was funded by grants from the Spanish Ministry of Economy and Competitiveness (BFU2010-16372), the Junta de Andalucía (CVI4567) and the European Union (FEDER). ; Peer reviewed

TDP-43 is a DNA and RNA binding protein involved in RNA processing and with structural resemblance to heterogeneous ribonucleoproteins (hnRNPs), whose depletion sensitizes neurons to double strand DNA breaks (DSBs). Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, in which 97% of patients are familial and sporadic cases associated with TDP-43 proteinopathies and conditions clearing TDP-43 from the nucleus, but we know little about the molecular basis of the disease. After showing with the non-neuronal model of HeLa cells that TDP-43 depletion increases R loops and associated genome instability, we prove that mislocalization of mutated TDP-43 (A382T) in transfected neuronal SHSY5Y and lymphoblastoid cell lines (LCLs) from an ALS patient cause R-loop accumulation, and R loop-dependent increased DSBs and Fanconi Anemia repair centers. These results uncover a new role of TDP-43 in the control of co-transcriptional R-loops and the maintenance of genome integrity by preventing harmful R-loop accumulation. Our findings thus link TDP-43 pathology to increased R-loops and R loop-mediated DNA damage opening the possibility that R-loop modulation in TDP-43-defective cells might help develop ALS therapies. ; Research in C.C's lab was funded by Fondazione Regionale per la Ricerca Biomedica for TRANS–ALS (Translating Molecular Mechanisms into ALS risk and patient's well-being: FRRB 2015- 0023) and in A.A.'s lab was funded by grants from the European Research Council (ERC2014- AdG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (BFU2016-75058- P), and the European Union (FEDER). A.B.F. was supported by a Juan de la Cierva-Formación fellowship (FJCI-2017-34536) from Spanish Ministry of Science and Innovation. M.G. was recipient of a scholarship provided by Erasmus+ Mobility for Traineeships from University of Pavia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

DNA double-strand breaks (DSBs) are one of the most dangerous DNA lesions, since their erroneous repair by nonhomologous end-joining (NHEJ) can generate harmful chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB ends that cannot be directly ligated due to their particular ability to bind to and insert nucleotides at the imperfect template-primer structures formed during NHEJ. Herein, we have devised genetic assays in yeast to induce simultaneous DSBs in different chromosomes in vivo. The repair of these breaks in trans could result in reciprocal chromosomal translocations that were dependent on classical Ku-dependent NHEJ. End-joining events leading to translocations were mainly based on the formation of short base pairing between 3′-overhanging DNA ends coupled to gap-filling DNA synthesis. A major proportion of these events were specifically dependent on yeast DNA polymerase Pol4 activity. In addition, we have discovered that Pol4-Thr540 amino acid residue can be phosphorylated by Tel1/ATM kinase, which could modulate Pol4 activity during NHEJ. Our data suggest that the role of Tel1 in preventing break-induced chromosomal translocations can, to some extent, be due to its stimulating effect on gap-filling activity of Pol4 to repair DSBs in cis. Overall, this work provides further insight to the molecular mechanisms of DSB repair by NHEJ and presents a new perspective to the understanding of how chromosomal translocations are formed in eukaryotic cells. © 2013 Ruiz et al. ; Spanish Ministry of Science and Innovation (BFU2009-10085, BFU2010-16370 and Consolider Ingenio 2010 CSD2007-015); European Union (FEDER); Spanish Council for Scientific Research (CSIC). ; Peer Reviewed

This is an open-access article distributed under the terms of the Creative Commons Attribution License. ; THO/TREX connects transcription with genome integrity in yeast, but a role of mammalian THO in these processes is uncertain, which suggests a differential implication of mRNP biogenesis factors in genome integrity in yeast and humans. We show that human THO depletion impairs transcription elongation and mRNA export and increases instability associated with DNA breaks, leading to hyper-recombination and γH2AX and 53BP1 foci accumulation. This is accompanied by replication alteration as determined by DNA combing. Genome instability is R-loop–dependent, as deduced from the ability of the AID enzyme to increase DNA damage and of RNaseH to reduce it, or from the enhancement of R-loop–dependent class-switching caused by THOC1-depletion in CH12 murine cells. Therefore, mammalian THO prevents R-loop formation and has a role in genome dynamics and function consistent with an evolutionary conservation of the functional connection between these mRNP biogenesis factors and genome integrity that had not been anticipated. ; This work was funded by grants from the Spanish Ministry of Science and Innovation (BFU2006-05260, BFU2010-16372, and Consolider Ingenio 2010 CSD2007-015), the Junta de Andalucía (BIO102, CVI624, and CVI4567), and the European Union (FEDER). ; Peer reviewed