Project description DEENESFRITPL 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. Show the project objective Hide the project objective 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 natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesearth and related environmental sciencesgeologymineralogycrystallographynatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2020 - Individual Fellowships Call for proposal H2020-MSCA-IF-2020 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator ECOLE NORMALE SUPERIEURE Net EU contribution € 184 707,84 Address 45, rue d'ulm 75230 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
