Objective
For cells and organisms to survive and propagate, they must accurately pass on their genetic information to the next generation. Errors in this process may arise from spontaneous mistakes in normal cellular metabolism, or from exposure to external agents, such as chemical mutagens and radiation. To protect themselves from the consequences of DNA damage, cells have evolved a vast array of pathways DNA repair mechanisms, each optimised for the resolution of a particular problem. One method of DNA repair, called homologous recombination (HR), involves using intact undamaged DNA sequences as a template to repair the damaged copy. HR is used extensively in meiotic cells to repair DNA breaks that are purposely created by the cell. In this context, HR is not just a repair mechanism, but also a method to drive interaction and genetic exchange between maternally and paternally inherited chromosomes, creating haploid genomes which are chimeras of the parental genetic information. Thus, the study of DNA repair and recombination informs our understanding of mechanisms that maintain genome stability, but which also generate genetic diversity, topics that are as critical to the survival of an individual cell as they are for the evolution and survival of an entire ecosystem. In recent decades a great deal has been learned of the genetic and biochemical control of the DNA repair and recombination mechanism. In general we infer gene function from what happens (or doesn’t happen) when we mutate a pathway of interest, and use biochemistry to test function using surrogate, simplified in vitro assays. Here, to bridge the divide between these classic approaches, I propose to develop biochemical methods using intact chromatin prepared from living cells. I believe that integrating chromatin biochemistry, with cell biology and genome-wide analysis will enable a new mode of scientific investigation, detailing how molecular reactions occur on biologically-relevant chromosomal substrates.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesbiochemistry
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesbiological sciencescell biology
- natural sciencesbiological sciencesgeneticschromosomes
- natural sciencesbiological sciencesgeneticsgenomes
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Call for proposal
ERC-2012-StG_20111109
See other projects for this call
Funding Scheme
ERC-SG - ERC Starting GrantHost institution
BN1 9RH Brighton
United Kingdom