Project description
Studying DNA motion at the atomic level
Emerging evidence indicates that DNA molecules have a conformational flexibility, which is an important attribute considering that DNA interacts with specific proteins. This flexibility is largely determined by the DNA sequence and is also central for gene expression. However, there is no information on the flexibility of DNA with lesions such as double-strand breaks. The scope of the EU-funded HRRinDNAwithSSB project is to study the dynamics of DNA flexibility and how motions occurring at the nanoscale influence this property. Results will help scientists understand the motions and flexibility of damaged DNA and unveil how it is repaired.
Objective
What role do conformational dynamics play in DNA function and repair? Structures of DNA show local dynamics, conformational flexibility of bases, and large conformational changes in the double helix, indicating easily accessible motions. Yet studying fast motions in nucleic acids is challenging. To address this we will introduce High Resolution Relaxometry (HRR) and apply it to study single strand breaks (SSBs) in DNA. Nucleic acids are often studied at atomic resolution with X-ray crystallography and high-field Nuclear Magnetic Resonance (NMR). Yet neither is suitable to study ns-motions. X-ray crystallography does not report on dynamics while using high-field NMR leads to high resonance frequencies so little ns time-scale information is present. This presents a challenge: how to characterise fast motions in nucleic acids? We will develop a new methodological approach, HRR, to probe ns-motions in DNA. HRR was developed by the host team to study ns-motions in proteins. We will adapt these methods to investigate motions in DNA. We will compare dynamics occurring in intact DNA, DNA with a SSB and SSB DNA with a missing base. Understanding the motions in each DNA construct will establish the effects that each type of DNA damage have on the motional properties of DNA. This will elucidate how each type of damage affects the base pair stacking and the motions occurring at the breakpoint. Understanding the flexibility induced by DNA damage will have a significant role in understanding DNA repair and how damaged DNA is recognised. The DNA repair protein, PARP-1, is a cancer-drug target and recognizes SSBs. Our final objective is to uncover the role of DNA motions in SSB recognition by PARP-1. In summary we will develop HRR as a new method to investigate ns-motions in DNA, providing a general approach to study ns-motions in nucleic acids at atomic resolution. We will discover the fundamental motions in DNA, how they are affected by SSBs and lead to recognition by PARP-1.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- natural sciences biological sciences genetics DNA
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75230 Paris
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.