Stephen Kearsey

Professor of Cell Biology

Tutorial Fellow, Keble College

 

Research Interests

My research group works on the regulation and mechanism of eukaryotic DNA replication, a process intrinsic to cell reproduction in all organisms. DNA replication is tightly regulated, only occurring in cells which are committed to divide. Replication starts from thousands of origins in the genome and several controls prevent origins from firing more than once per cell cycle, thus ensuring that only two copies of each chromosome are produced. The amazing fidelity of the copying process (one error per 109 nucleotides) is ensured in part by checkpoint mechanisms that delay replication if DNA is damaged and repair mechanisms which fix replication errors. Genome instability can result from defects in DNA replication and this is a factor in cancer development.

Most of our research uses fission yeast (Schizosaccharomyces pombe). This model organism has a similar mechanism of DNA replication to that found in mammalian cells, but is amenable to sophisticated genetic and cell biological techniques. For further details on research projects see my lab web pages. Information on the process of DNA replication can be found at www.dnareplication.net.

 

Contacts

Email: stephen.kearsey@zoo.ox.ac.uk
 
 

Selected Publications

  • Guarino, E., I. Salguero, and S.E. Kearsey. (2014) Cellular regulation of ribonucleotide reductase in eukaryotes. Seminars in cell & developmental biology. 30:97-103.

  • Palles,  et al. (2013) Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nature genetics. 45:136-144.

  • Hua, H., M. Namdar, O. Ganier, J. Gregan, M. Mechali, and S.E. Kearsey. (2013) Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis. Molecular biology of the cell. 24:578-587.

  • Havens et al. (2012) Direct role for proliferating cell nuclear antigen in substrate recognition by the E3 ubiquitin ligase CRL4Cdt2. The Journal of biological chemistry. 287:11410-11421.

  • Salguero, I., E. Guarino, M.E. Shepherd, T.D. Deegan, C.G. Havens, S.A. MacNeill, J.C. Walter, and S.E. Kearsey. (2012) Ribonucleotide reductase activity is coupled to DNA synthesis via proliferating cell nuclear antigen. Current biology : CB. 22:720-726.

  • Tvegard, T., Soltani, H., Skjolberg, H.C., Krohn, M., Nilssen, E.A., Kearsey, S.E., Grallert, B. and Boye, E. (2007) A novel checkpoint mechanism regulating the G1/S transition. Genes Dev, 21, 649-654.

  • Ralph, E., Boye, E. and Kearsey, S.E. (2006) DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1. EMBO Rep, 7, 1134-1139.

  • Kearsey, S. and Cotterill, S. (2003) Enigmatic variations: divergent modes of regulating eukaryotic DNA replication. Molecular Cell, 12, 1067-1075.