Dr Nicholas A. Kent - DPhil
DNA in eukaryotic cells does not function as a naked molecule but is packaged into a nucleoprotein complex called chromatin. Chromatin has several functions: it maintains the solubility of DNA within the confines of the cell nucleus; it provides the basis for a hierarchical system of compaction steps which physically organise chromosomes; it is a substrate for the application of a huge variety of epigenetic molecular marks. As the substrate on which the mechanisms of DNA transcription, replication, repair and segregation operate, it often plays a key role in the regulation of chromosome function. Defects in chromatin structure and remodelling are now emerging as critical causal factors in a variety of disease processes including cancer.
The Kent Lab studies the enzymes and DNA-binding proteins which act at the level of the basic subunit of chromatin, the nucleosome. The nucleosome is a complex of 146 base pairs of DNA wrapped approximately twice around a compact protein core consisting of two copies of each of histone H2A, H2B, H3 and H4. Eukaryotic DNA is wrapped repeatedly into nucleosomes forming a beads-on-a-string arrangement.
Three views of the nucleosome core particle (from PDB 1kx5)
Interestingly, nucleosomes are not placed randomly with respect to the underlying DNA and many appear to be deliberately positioned. The Kent Lab is particularly interested in the factors which put nucleosomes into the "right place", slide nucleosomes into new positions or remove them from DNA completely. We use budding yeast as a model eukaryotic system together with a variety of state-of-the-art chromatin analysis techniques to identify and characterise these chromatin remodellers, and to discover their functions in gene regulation and DNA repair.
Positioned nucleosomes in the yeast genome mapped using next-generation DNA sequencing (Kent et al., 2010)
Collaborations
Dr. Jessica Downs - Sussex UK.
Prof. Adrian Harwood - Cardiff UK
Dr. Jane Mellor - Oxford UK
Prof. Nick Proudfoot FRS - Oxford UK
Prof. Ray Waters - Cardiff UK