Chromatin and maintenance of genome stability
Within eukaryotes, DNA is packaged into chromatin. The basic unit of chromatin is the nucleosome, formed by the wrapping of ~147 bp of DNA around an octamer of histones proteins. Efficient DNA repair requires manipulation of chromatin to facilitate DNA processing and permit repair enzymes access to sites of damage. These changes to chromatin organisation include covalent modification of histone proteins, incorporation of histone variants and ATP-dependent chromatin remodelling and defects in these processes can result in genome instability, one of the hallmarks of cancer cells.
The focus of our research group is to understand the role of chromatin and ATP-dependent chromatin remodelling complexes in maintenance of genome stability. Several chromatin remodelling complexes are associated with repair and their involvement is evolutionarily conserved from yeast to humans. We are using both mammalian and yeast systems as well as in vitro assays to investigate the role of chromatin remodelling in maintenance of genome stability and elucidate mechanistic detail of how chromatin remodelling protects genome integrity. By gaining a more complete understanding of the role that chromatin remodelling plays in safeguarding the genome, we aim to gain information that can be used to design and inform cancer therapies and reveal novel drug targets. Prospective students should get in touch for further details of potential graduate student projects for the coming year.
 Chambers AL, Downs JA. The RSC and INO80 chromatin-remodeling complexes in DNA double-strand break repair. Prog Mol Biol Transl Sci. 2012;110:229-61. (review)
 Chambers AL, Ormerod G, Durley SC, Sing TL, Brown GW, Kent NA, Downs JA. The INO80 chromatin remodeling complex prevents polyploidy and maintains normal chromatin structure at centromeres. Genes Dev. 2012 Dec 1;26(23):2590-603.
 Brownlee PM, Chambers AL, Cloney R, Bianchi A, Downs JA. BAF180 promotes cohesion and prevents genome instability and aneuploidy. Cell Rep. 2014 Mar 27;6(6):973-81.