- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Light effects on plants
- CRISPR and Genetic Engineering
- Plant Genetic and Mutation Studies
- Plant Molecular Biology Research
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Stress Responses and Cortisol
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Photosynthetic Processes and Mechanisms
- Genetic Associations and Epidemiology
- DNA and Nucleic Acid Chemistry
- Hypothalamic control of reproductive hormones
- Pluripotent Stem Cells Research
- Fungal and yeast genetics research
- Cancer-related Molecular Pathways
- Neurology and Historical Studies
- Plant Reproductive Biology
Centro de Biología Molecular Severo Ochoa
2016-2025
Universidad Autónoma de Madrid
2016-2025
Centro de Estudios Fotosintéticos y Bioquímicos
2018-2024
Consejo Superior de Investigaciones Científicas
2008-2023
Instituto de Física Teórica
2023
National University of Rosario
2018-2021
University of Cambridge
2021
Stony Brook University
2018
Steno Diabetes Centers
2018
Instituto de Biología Funcional y Genómica
2011
Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity our genome. Here we combine genome-wide approach to identify preferential sites initiation at 0.4% mouse genome with detailed molecular analysis distinct classes ORIs according their location relative genes. Our study reveals that 85% embryonic stem (ES) cells are associated transcriptional units. Nearly half identified map promoter regions and, interestingly,...
Chromatin is the template for basic processes of replication and transcription, making maintenance chromosomal integrity critical cell viability. To elucidate how dividing cells respond to alterations in chromatin structure, here we analyse programme primary with altered configuration caused by genetic ablation HMGB1 gene, or three histone H1 genes. We find that loss compaction H1-depleted triggers accumulation stalled forks DNA damage as a consequence transcription-replication conflicts. In...
The unanticipated widespread occurrence of stable hybrid DNA/RNA structures (R-loops) in human cells and the increasing evidence their involvement several malignancies have invigorated research on R-loop biology recent years. Here we propose that physiological formation at CpG island promoters can contribute to DNA replication origin specification these regions, most efficient initiation sites mammalian cells. Quite likely, this occurs by strand-displacement reaction activating G-quadruplex...
UV-B is a high-energy component of the solar radiation perceived by plant and induces number modifications in growth development, including changes flowering time. However, molecular mechanisms underlying these are largely unknown. In present work, we demonstrate that Arabidopsis plants grown under white light supplemented with show delay time, this developmental reprogramming mediated UVR8 photoreceptor. Using combination gene expression analyses irradiation different mutants, gained...
Abstract Cells must coordinate the activation of thousands replication origins dispersed throughout their genome. Active transcription is known to favor formation mammalian origins, although role that RNA plays in this process remains unclear. We show ORC1 subunit human Origin Recognition Complex interacts with RNAs transcribed from genes start sites (TSSs), displaying a positive correlation between binding and origin activity. depletion, or use RNA-binding mutant, result inefficient...
DNA replication origins (ORIs) map close to promoter regions in many organisms, including mammals. However, the relationship between initiation of and transcription is not well understood. To address this issue, we have analyzed timing activity several CpG island-associated ORIs on transcriptionally active silent X chromosomes. We find equivalent ORI usage efficiency both alleles at sites that are replicated late inactive chromosome. Thus, contrast its repressive effect transcription,...
Linker histones are highly abundant chromatin-associated proteins with well-established structural roles in chromatin and as general transcriptional repressors. In addition, it has been long proposed that histone H1 exerts context-specific effects on gene expression. Here, we identify a function of structure transcription using range genomic approaches. the absence H1, there is an increase non-coding RNAs, together reduced levels m6A modification leading to their accumulation causing...
The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report role in chromatin organization during unperturbed conditions, catalytic-independent manner. lack leads to abnormalities nuclear and nucleolar morphology, alters replication timing increases transcription....
Most cellular proteins involved in genome replication are conserved all eukaryotic lineages including yeast, plants and animals. However, the mechanisms controlling their availability during cell cycle less well defined. Here we show that Arabidopsis encodes for two ORC1 highly similar amino acid sequence have partially overlapping expression domains but with distinct functions. The ancestral ORC1b gene, present before partial duplication of genome, has retained canonical function DNA...
DNA replication origins (ORI) are regulatory regions from which the genome is replicated once every cell cycle. A widely used method for their identification in mammalian chromosomes relies on quantitative PCR of nascent strands across candidate regions. We developed a new high-resolution strategy to localize ORIs directly total unfractionated human DNA. The increase sensitivity provided by this approach has revealed that short region ∼200-base-pair overlapping well-characterized undergoes...
Summary UV ‐B radiation inhibits plant growth, and this inhibition is, to a certain extent, regulated by miR396‐mediated repression of Growth Regulating Transcription factors ( GRF s). Moreover, E2Fe transcription factor also modulates Arabidopsis leaf growth. Here, we provide evidence that, at intensities that induce DNA damage, E2Fc participates in the cell proliferation. We demonstrate ‐deficient plants show lower size under conditions damage , decreased death after exposure altered SOG 1...
In mammalian cells, chromosomal replication starts at thousands of origins which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' whose genomic distribution and regulation not well understood. this study, we have analyzed origin activity in mouse embryonic stem cells the absence or presence mild replicative induced by aphidicolin, a DNA polymerase inhibitor, deregulation licensing factor CDC6. both cases, observe that majority...
In female mammals, one of the two X chromosomes is inactivated to compensate for difference in dosage X-linked genes between males and females. inactivation involves sequential alterations chromatin that ultimately lead transcriptional repression on chromosome. Here, histone methylation acetylation along are investigated by immunoprecipitation (ChIP) adult fibroblast cell lines. At <i>Pgk1</i> <i>Hprt,</i> active chromosome reveals H3 lysine 4 histones H4. These...
Robustness and completion of DNA replication rely on redundant origins. Reduced efficiency origin licensing is proposed to contribute chromosome instability in CDK-deregulated cell cycles, a frequent alteration oncogenesis. However, the mechanism by which this occurs largely unknown. Current models suggest that limited numbers would reduce fork density favouring rearrangements, but experimental support cells lacking. We have investigated pattern firing budding yeast lacking CDK regulators...
The replication program of vertebrate genomes is driven by the chromosomal distribution and timing activation tens thousands origins. Genome-wide studies have shown association origins with promoters CpG islands, their enrichment in G-quadruplex motifs (G4). However, genetic determinants driving activity remain poorly understood. To gain insight on constraints operating origins, we conducted first evolutionary comparison across vertebrates. We generated a genome-wide map chicken (the bird...