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Structural Biology Programme

Macromolecular Complexes in DNA Damage Response Group

Group Leader:  Óscar Llorca
Research highlights

a) Structural and molecular mechanisms regulating PIKK kinases.

Our group has contributed to the structural analysis of several members of the PIKK family, mostly DNA-PKcs and SMG1. We are now focused on understanding how additional partners regulate PIKK kinase activity as part of larger complexes.

b) Molecular chaperones in cancer.

We are currently studying HSP90-mediated assembly of PIKKs. This project is performed in collaboration with Laurence H. Pearl (Genome Damage and Stability Centre, University of Sussex, UK). We are also interested in how the R2TP complex participates in the maturation of other complexes of relevance in cancer, as well as the role in these pathways of RuvBL1 and RuvBL2. These are two conserved ATPases essential for the activity of several macromolecular assemblies, including R2TP and complexes involved in chromatin remodelling.

c) Photochemical trap and high-resolution imaging of transient chromatin complexes from living cells.

We have been awarded an HFSP-2017 research grant. Coordinator: O. Llorca; Partners: Heinz Neumann (MPI, Germany), Mark Skehel (LMB-MRC, UK). The goal is to chemically trap in vivo chromatin-remodelling complexes on chromatin, image their structure by cryo-EM and define their in vivo post-transcriptional modifications associated with each structure and functional state. This project is performed in collaboration with Fabrizio Martino, Junior PI at the CIB-CSIC.