Many proteins involved in protecting and precisely propagating the genome are directly recruited to chromatin and chromosomes. Although many proteins involved in these processes are known, many more are likely to be involved. We have developed technology for proteomic analysis of chromatin in defined cell cycle states using Xenopus extracts. We are using this methodology to identify novel chromatin components which we have shown play critical roles in cell cycle progression. We are investigating proteins that are specifically recruited to chromatin in certain cell cycle states, including proteins induced by specific cell cycle inhibitors, DNA damaging agents and by chemotherapeutic drugs. For a selection of interesting proteins, we will perform functional studies to determine their contribution to the maintenance of genomic integrity, using both Xenopus extracts and human tissue culture cells. Some of the new proteins that we identify may be lost in cancer cells, and have potential as diagnostic/prognostic markers or as targets for novel anti-cancer treatments.
Gillespie, P.J., Khoudoli, G.K., Stewart, G., Swedlow, J.R. and Blow, J.J. (2007). ELYS/MEL-28 chromatin association coordinates nuclear pore complex assembly and the replication licensing system. Curr. Biol. 17, 1657–1662. [abstract]
Porter, I.M., McClelland, S., Khoudoli, G.A., Hunter, C.J., Andersen, J.S., McAinsh, A.D., Blow, J.J. and Swedlow, J.R. (2007). Bod1, a novel centrosome and kinetochore protein required for chromosome biorientation. J. Cell Biol., 179, 187-197. [Faculty of 1000 Recommendation] [abstract]
Khoudoli, G.A., Gillespie, P.J., Stewart, G., Andersen, J.S., Swedlow, J.R. and Blow, J.J. (2008). Temporal profiling of the chromatin proteome reveals system-wide responses to replication inhibition. Curr Biol 18, 838-843. [abstract]
Gambus, A., Khoudoli, G.A., Jones, R.C. and Blow, J.J. (2011). Mcm2-7 form double hexamers at licensed origins in Xenopus egg extract. J. Biol. Chem. 286, 11855-64. [abstract]
Moser, S.C., Bensaddek, D., Ortmann, B., Mudie, S., Blow, J.J., Lamond, A.I., Swedlow, J.R. and Rocha, S. (2013). PHD1 links cell-cycle progression to oxygen sensing through hydroxylation of the centrosomal protein Cep192. Dev. Cell 26, 381-92. [abstract] [pdf]