David Lilley - Overview

The central goal of the research of this laboratory is to understand the structure, folding and function of branched nucleic acid structures. Structures like the four-way (Holliday) junction are important elements in the recombination and repair of DNA. We have elucidated the structure of the four-way junction, and much of our present work is directed towards the way it is recognised by a group of structure-selective proteins, the junction-resolving enzymes. These proteins are widespread, from bacteriophage to mammals, and divide into two main superfamilies. We are studying many of these, and have recently solved the crystal structure of one. Branchpoints are also important architectural elements in RNA structure. We are studying the general conformational principles of these elements. RNA also exhibits catalytic activity, and these ribozymes are frequently constructed around such junctions. Ribozyme activity is important for some of the most basic cellular reactions, including protein synthesis, and we are interested in the chemical origins of these processes. We are studying the structure, folding and activity of three nucleolytic ribozymes.