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Genome Maintenance in the Context of Chromatin

Objective

With the availability of the essentially complete sequence of the human genome, as well as a rapid development of massive sequencing techniques, the research efforts to understand genetics and disease from a cis standpoint will soon reach an endpoint. However, our emerging knowledge of gene regulation networks reveals that epigenetic regulation of the hereditary information plays crucial roles in various biological events through its influence on processes such as transcription, DNA replication and chromosome architecture. Another scenario in which the control of chromatin structure is crucial is the repair of lesions in genomic DNA. There is mounting evidence, particularly from model organisms such as Saccharomyces cerevisiae, that histone modifying enzymes (acetylases, deacetylases, kinases, …) are essential components of the machinery that maintains genome integrity and thereby guards against cancer, degenerative diseases and ageing. However, little is known about the specific “code” of histone tail modifications that coordinate DNA repair, and the impact that an aberrant “histone code” may have on human health. In CHROMOREPAIR we will systematically analyze the chromatin remodelling process that undergoes at DNA lesions and evaluate the impact that chromatin alterations have on the access, signaling and repair of DNA damage. Furthermore, we propose to translate our in vitro knowledge to the development of mouse models that help us evaluate how modulation of chromatin status impinges on genome maintenance and therefore on cancer and aging. As a provocative line of research and based on our preliminary data, we propose that certain chromatin alterations could not only impair but also in some cases promote a more robust response to DNA breaks, which could be a novel and not yet explored way to potentiate the elimination of pre-cancerous cells.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /natural sciences/biological sciences/genetics and heredity/dna
  • /medical and health sciences/clinical medicine/cancer

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
Address
Calle Melchor Fernandez Almagro 3
28029 Madrid
Spain
Activity type
Research Organisations
EU contribution
€ 948 426
Principal investigator
Oscar Fernández-Capetillo Ruiz (Dr.)
Administrative Contact
Dolores Liebanes (Dr.)

Beneficiaries (1)

FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
Spain
EU contribution
€ 948 426
Address
Calle Melchor Fernandez Almagro 3
28029 Madrid
Activity type
Research Organisations
Principal investigator
Oscar Fernández-Capetillo Ruiz (Dr.)
Administrative Contact
Dolores Liebanes (Dr.)