Cell biology and Biotechnology

Nuclear Architecture and Dynamics


One of the current challenges of cell biology in the postgenomic era is to understand how the DNA is organized in the 3D nuclear space and how this organization contributes to essential cellular processes such as gene expression, DNA repair or chromosome segregation. Changes in nuclear architecture correlates with developmental and differentiation processes and defects in architectural elements are responsible for several human diseases.
Our lab uses the fission yeast Schizosaccharomyces pombe as eukaryotic model organism. In this yeast, chromosomes are anchored to the nuclear envelope via specific DNA loci such as centromeres, telomeres and TFIIIC binding sites. This remarkable topological organization requires the presence of distinct DNA sequences and chromatin domains and relies on a large number of proteins that mediate chromatin interactions with the nuclear envelope. Therefore, the nuclear envelope serves as a dynamic scaffold to anchor and organize distinct chromosomal domains, thus generating a higher-order nuclear architecture. 
Fission yeast nuclear organisation shares many features with that of more complex nuclei of higher eukaryotes. These features include large repeat-rich centromeres and peripherally localised heterochromatin relying on RNAi-dependent pathway. This, in combination with a small 13.8 Mb genome, just three chromosomes and a relatively large nucleus (2.5-3 µm in diameter), suitable for microscopic observation, makes fission yeast a convenient tool for understanding conserved principles underlying eukaryotic nuclear organisation and function. Both fission yeast and metazoans possess evolutionarily conserved physical links between the DNA and the nuclear envelope that contribute to creating and maintaining nuclear architecture. Such links are prominent at centromeric and telomeric heterochromatin but are also found at a large number of other sites within the fission yeast genome.
Our lab uses a combination of yeast genetics, molecular biology, live cell microscopy and physical manipulation of the nucleus to study mechanisms regulating the spatial organization of the fission yeast nucleus and genome, and the implications behind this organization in chromosome segregation.

CABD - Centro Andaluz de Biología del Desarrollo

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