Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)
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What causes an RNA-DNA hybrid to compromise genome integrity? [Article]
(Elsevier, 2019)Transcription is a source of genome instability that stimulates mutation and recombination. Part of the damage produced by transcription is mediated by R-loops, non-B DNA structures that normally form by the re-annealing ...
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R Loops: From Physiologicalto Pathological Roles [Article]
(Elsevier, 2019-10-17)DNA-RNA hybrids play a physiological role in cellular processes, but often, they represent non-scheduled co-transcriptional structures with a negative impact on transcription, replication and DNA repair. Accumulating ...
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The DNA damage response acts as a safeguardagainst harmful DNA–RNA hybrids ofdifferent origins [Article]
(EMBO Press, 2019-07-24)Despite playing physiological roles in specific situations, DNA–RNA hybrids threat genome integrity. To investigate how cells do counteract spontaneous DNA–RNA hybrids, here we screen an siRNA library covering 240 human ...
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Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability [Article]
(Elsevier, 2019)Although correlations between RNA polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established, the mechanisms underlying these connections remain poorly understood. Here, we used a ...
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Homologous Recombination: To Fork and Beyond [Article]
(MDPI, 2018)Accurate completion of genome duplication is threatened by multiple factors that hamper the advance and stability of the replication forks. Cells need to tolerate many of these blocking lesions to timely complete DNA ...
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Transcription-mediated replication hindrance: a major driver of genome instability [Article]
(Cold Spring Harbor Laboratory Press, 2019)Genome replication involves dealing with obstacles that can result from DNA damage but also from chromatin alterations, topological stress, tightly bound proteins or non-B DNA structures such as R loops. Experimental ...
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Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion [Article]
(Nature Research, 2019)Genome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid ...
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Human Mesenchymal Stem Cells Prevent Neurological Complications of Radiotherapy [Article]
(Frontiers Media S.A., 2019-05-16)Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life ...
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Oestrogen receptor β mediates the actions of bisphenol-A on ion channel expression in mouse pancreatic beta cells [Article]
(Springer Nature, 2019-09)Aims/hypothesis: Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical that has been associated with type 2 diabetes development. Low doses of BPA modify pancreatic beta cell function and induce insulin resistance; ...
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The Cornelia de Lange Syndrome-associated factor NIPBL interacts with BRD4 ET domain for transcription control of a common set of genes [Article]
(Springer Nature, 2019-07-18)Mutations in NIPBL are the major cause of Cornelia de Lange Syndrome (CdLS). NIPBL is the cohesin-loading factor and has recently been associated with the BET (bromodomains and extra-terminal (ET) domain) proteins BRD2 and ...
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Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability [Article]
(Elsevier, 2019)THO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein ...
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Non-canonical replication initiation: You’re fired! [Article]
(Multidisciplinary Digital Publishing Institute (MDPI), 2017)The division of prokaryotic and eukaryotic cells produces two cells that inherit a perfect copy of the genetic material originally derived from the mother cell. The initiation of canonical DNA replication must be coordinated ...
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Histone Mutants Separate R Loop Formation from Genome Instability Induction [Article]
(Elsevier, 2017)R loops have positive physiological roles, but they can also be deleterious by causing genome instability, and the mechanisms for this are unknown. Here we identified yeast histone H3 and H4 mutations that facilitate R ...
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Late rDNA Condensation Ensures Timely Cdc14 Release and Coordination of Mitotic Exit Signaling with Nucleolar Segregation [Article]
(Elsevier, 2017)The nucleolus plays a pivotal role in multiple key cellular processes. An illustrative example is the regulation of mitotic exit in Saccharomyces cerevisiae through the nucleolar sequestration of the Cdc14 phosphatase. The ...
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Human THO–Sin3A interaction reveals new mechanisms to prevent R-loops that cause genome instability [Article]
(Wiley-Blackwell, 2017)R-loops, formed by co-transcriptional DNA–RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent ...
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The Nup84 complex coordinates the DNA damage response to warrant genome integrity [Article]
(Oxford University Press, 2019)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 ...
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Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways [Article]
(Shared Science Publishers OG, 2019)Understanding the plasticity of genomes has been greatly aided by assays for recombination, repair and mutagenesis. These assays have been developed in microbial systems that provide the advantages of genetic and molecular ...
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Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways [Article]
(Shared Science Publishers, 2019)Understanding the plasticity of genomes has been greatly aided by assays for recombination, repair and mutagenesis. These assays have been developed in microbial systems that provide the advantages of genetic and molecular ...
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TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling [Article]
(Frontiers Media, 2019)Calcium is an important second messenger required not only for the excitation-contraction coupling of the heart but also critical for the activation of cell signaling pathways involved in the adverse cardiac remodeling and ...
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BRCA1 Accelerates CtIP-Mediated DNA-End Resection [Article]
(Elsevier, 2014)DNA-end resection is a highly regulated and critical step in the response and repair of DNA double-strand breaks. In higher eukaryotes, CtIP regulates resection by integrating cellular signals via its posttranslationa ...