Dragana Ahel

SNF2 ATPases in genome stability and cancer

The maintenance of complete and undamaged genome is critical for survival. Because DNA is continuously exposed to genotoxic stress, cells have evolved different mechanisms that are specialised for correcting different types of DNA damage. These mechanisms play critical roles in the maintenance of genome integrity, and their deficiencies have been associated with ageing and cancer.

We are particularly interested in a family of proteins called SNF2 ATPases. SNF2 ATPases are a heterogeneous family, whose members regulate a variety of nuclear functions (including chromatin remodelling, transcription, DNA replication, DNA repair and recombination). Interestingly, a significant number of SNF2 ATPases have been associated with human disease and cancer, which highlights their biological relevance.

Our recent focus has been on two SNF2 family members, ALC1 and ZRANB3. Our previous work identified ALC1 and ZRANB3 proteins as novel DNA repair factors with associated functions in chromatin remodelling and DNA replication, respectively. This work also provided new insights into the roles of specific protein post-translational modifications (poly(ADP-ribosyl)ation and polyubiquitination) in cellular response to DNA damage and replication stress.

We use a multidisciplinary approach to study SNF2 ATPases at a biochemical, cellular, and physiological level. Our aim is to provide a detailed picture of their function and improve our understanding of fundamental cellular mechanisms that impact on genome stability and play a role in human disease.

Relevant Publications

Sharifi,R, Morra,R, Denise Appel,C, Tallis,M, Chioza,B, Jankevicius,G, Simpson,M.A, Matic,I, Ozkan,E, Golia,B, Schellenberg,M.J, Weston,R, Williams,J.G, Rossi,M.N, Galehdari,H, Krahn,J, Wan,A, Trembath,R.C, Crosby,A.H, Ahel,D, Hay,R, Ladurner,A.G
2013

EMBO J. 32: 1225-37

Mehrotra, P.V., Ahel, D., Ryan, D.P., Weston, R., Wiechens, N., Kraehenbuehl, R., Owen-Hughes, T., and Ahel, I.
2011

Mol Cell 41: 46-55.

Ahel, D., Horejsí, Z., Wiechens, N., Polo, S.E., Garcia-Wilson, E., Ahel, I., Flynn, H., Skehel, M., West, S.C., Jackson, S.P., Owen-Hughes, T., Boulton, S.J.
2009

Science 325: 1240-1243.

dragana.ahel@path.ox.ac.uk

Research Areas