Objective
Here, I propose to unravel the molecular mechanisms that regulate TLS during DNA damage bypass through advanced complementary approaches.
Thousands of DNA damaging insults are inflicted daily upon the genomes of all living cells. If left unrepaired, these lesions can be life-threatening for organisms as they alter the content and organization of the genetic material. To overcome this constant challenge, cells are equipped with a global DNA damage response that impacts on diverse cellular processes to facilitate reestablishment of genome integrity. The genome is particularly vulnerable to DNA damage during DNA replication, where DNA is precisely duplicated as part of the cell division process. Translesion DNA synthesis (TLS), mediated by specialized low-fidelity DNA polymerases, is an important cellular mechanism for preventing gross chromosomal instability following DNA damage encountered during DNA replication. However, our understanding of how this is achieved at the molecular level remains surprisingly limited.
First, in combination with state-of-the-art mass spectrometry facilities present at the CPR, I will set up a newly established screening method, termed BioID, for efficient, unbiased identification of novel proteins that specifically act at replication forks during TLS. Second, I will mine proteomic screens for DNA damage-regulated ubiquitylation for novel TLS-regulating factors. From these screens I will select the most promising candidate proteins for further validation and characterization of their potential roles in TLS regulation. I will study how these proteins impact on TLS by establishing cell lines capable of overexpressing or knocking down each factor, and employ these in a panel of biochemical and cell-based methods established in the host lab.
This project will advance our understanding of the molecular mechanisms that control and integrate TLS activity with genome integrity maintenance.
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
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences genetics genomes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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-2012-IEF
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Funding Scheme
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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
1165 KOBENHAVN
Denmark
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