Objective
Our cells are faced with thousands of DNA lesions every day. Failure to repair such lesions can lead to genomic instability, cancer development or cell death. Repair of DNA damage, however, is complicated by the fact that genomic DNA is packaged, through histone and non-histone proteins, into a condensed structure called chromatin. Recently, an increasing interest on the impact of chromatin and the epigenetic changes that occur in DNA damage repair has emerged. Nevertheless, the functional interplay between damage-induced interference of transcription and modulation of chromatin to allow accessibility of DNA lesions by the repair machineries is still an enigma. Here, I propose biochemical and genetic approaches complemented with advanced proteomic and genome wide technologies to i) isolate and characterise the chromatin remodelling factors that functionally interact with damage arrested RNA Polymerase II/repair complexes in response to genotoxic stress. Focus will be on potential differences in the composition of protein complexes and their posttranslational modifications in normal human cells and in patient-derived repair deficient cells. ii) To decode the epigenetic changes that occur in response to DNA damage at genome wide level and in the vicinity of transcription blocking DNA lesions. iii) To elucidate the role of key repair and chromatin factors on transcription-mediated DNA damage response and study their interplay with damage signaling proteins (such as protein kinases, ubiquitin ligases, and histone methylases/acetyltransferases).
These studies are expected to increase our understanding on the impact of chromatin function-structure and the histone modifications that occur upon genotoxic stress and change transiently the plasticity of chromatin structure, linking persistent damage in active genes to repair, cell cycle arrest or apoptosis in mammalian cells. In addition, this knowledge may lead to the identification of targets for therapeutic intervention.
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 sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-IEF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
16 672 VARI-ATHENS
Greece
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