Structural Studies Of DNA and RNA Transactions
Our studies of nucleic acid transactions have been most powerful at defining the overall architecture of a large number of macromolecular assemblies involved in the critical initiation steps in DNA replication, RNA transcription and translation, for which no crystallographic information yet exist (e.g. ORC, TFIID, eIF3), as well as putting the crystal structures of essential elements in RNA processing and degradation in the complex of fully functional complexes (e.g. exosome, RLC). Our aim is to gain mechanistic insight that goes beyond overall architecture, by pushing resolution, describing conformational landscapes, and relating structural states to function via the analysis of interactions with ligands and regulatory factors.
Eukaryotic DNA Replication
During cell division, initiator proteins target and bind to DNA replication origins to trigger genome duplication. We are characterizing the structure of Drosophila melanogaster Origin Recognition Complex (DmORC), and the effect of nucleotide and phosphorylation state in conformation and function ... read more about ORC ...
Regulated gene transcription in eukaryotes requires the assembly of a complex molecular machinery that includes general factors, activators, cofactor complexes and chromatin modifying and remodeling factors. We are interested in characterizing the structure of these different components and how they interact to regulate transcription. Read more about chromatin remodelers ... Read more about TFIID ... Read more about RNAPII... Read more about PRC2...
Eukaryotic Translation Initiation
In eukaryotes at least twelve translation initiation factors and an mRNA methylated G-cap are required to initiate protein synthesis, while in many viruses a structured RNA element replaces most of those factors. We are studying the molecular interplays that characterize both initiation pathways ... read more about eIF3
Transcription-Coupled DNA Repair
Our lab is part of a large NCI funded project in Structural Biology of DNA Repair that aims at producing biologically relevant DNA repair structures and identifying fundamental structural principles for repair proteins. The role of electron microscopy is to provide structures of large macromolecular complexes involved in these processes... read more