Kearsey Lab

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Kearsey Lab

About the Group

My research group works on the maintenance of genome stability. Genome stability is maintained by high fidelity of DNA replication coupled with DNA repair mechanisms that together lead to amazing fidelity in the copying process (one error per 109 nucleotides). Mismatch correction mechanisms rectify nucleotide misincorporation errors occurring during DNA synthesis and multiple repair pathways fix DNA damage caused by endogenous and exogenous factors.  DNA repair pathways are backed up by checkpoint mechanisms that halt the cell cycle or initiate apoptosis following DNA damage or chromosome segregation errors. Genome instability that results from defects in DNA replication, repair or checkpoint pathways can be 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.

Members

Professor Stephen Kearsey

Post-docs:
Dr Nagore De León
Dr Ignacio Soriano

Graduate students:
Sibyl Bertrand
Emily Rayner
Sophia Toumazou

Recent Publications

Pai, C.C., A. Kishkevich, R.S. Deegan, A. Keszthelyi, L. Folkes, S.E. Kearsey, N. De Leon, I. Soriano, R.A.M. de Bruin, A.M. Carr, and T.C. Humphrey. 2017. Set2 Methyltransferase Facilitates DNA Replication and Promotes Genotoxic Stress Responses through MBF-Dependent Transcription. Cell Rep. 20:2693-2705.

Pai, C.C., and S.E. Kearsey. 2017. A Critical Balance: dNTPs and the Maintenance of Genome Stability. Genes (Basel). 8.

Rayner, E., I.C. van Gool, C. Palles, S.E. Kearsey, T. Bosse, I. Tomlinson, and D.N. Church. 2016. A panoply of errors: polymerase proofreading domain mutations in cancer. Nat Rev Cancer. 16:71-81.

Aoude, L.G., E. Heitzer, P. Johansson, M. Gartside, K. Wadt, A.L. Pritchard, J.M. Palmer, J. Symmons, A.M. Gerdes, G.W. Montgomery, N.G. Martin, I. Tomlinson, S. Kearsey, and N.K. Hayward. 2015. POLE mutations in families predisposed to cutaneous melanoma. Fam Cancer. 14:621-628.

Guarino, E., I. Salguero, and S.E. Kearsey. 2014. Cellular regulation of ribonucleotide reductase in eukaryotes. Semin Cell Dev Biol. 30:97-103.

Guarino, E., G. Cojoc, A. Garcia-Ulloa, I.M. Tolic, and S.E. Kearsey. 2014. Real-time imaging of DNA damage in yeast cells using ultra-short near-infrared pulsed laser irradiation. PLoS One. 9:e113325.

Palles, C., J.B. Cazier, K.M. Howarth, E. Domingo, A.M. Jones, P. Broderick, Z. Kemp, S.L. Spain, E. Guarino, I. Salguero, A. Sherborne, D. Chubb, L.G. Carvajal-Carmona, Y. Ma, K. Kaur, S. Dobbins, E. Barclay, M. Gorman, L. Martin, M.B. Kovac, S. Humphray, C. Consortium, W.G.S. Consortium, A. Lucassen, C.C. Holmes, D. Bentley, P. Donnelly, J. Taylor, C. Petridis, R. Roylance, E.J. Sawyer, D.J. Kerr, S. Clark, J. Grimes, S.E. Kearsey, H.J. Thomas, G. McVean, R.S. Houlston, and I. Tomlinson. 2013. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 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. Mol Biol Cell. 24:578-587.

Church, D.N., S.E. Briggs, C. Palles, E. Domingo, S.J. Kearsey, J.M. Grimes, M. Gorman, L. Martin, K.M. Howarth, S.V. Hodgson, N. Collaborators, K. Kaur, J. Taylor, and I.P. Tomlinson. 2013. DNA polymerase epsilon and delta exonuclease domain mutations in endometrial cancer. Hum Mol Genet. 22:2820-2828.

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. Curr Biol. 22:720-726.

Pai, C.C., J. Schnick, S.A. MacNeill, and S.E. Kearsey. 2012. Conditional inactivation of replication proteins in fission yeast using hormone-binding domains. Methods. 57:227-233.

Havens, C.G., N. Shobnam, E. Guarino, R.C. Centore, L. Zou, S.E. Kearsey, and J.C. Walter. 2012. Direct role for proliferating cell nuclear antigen in substrate recognition by the E3 ubiquitin ligase CRL4Cdt2. J Biol Chem. 287:11410-11421.

List of site pages