Stephen Kearsey 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.
Currently Stephen Kearsey’s research group is working on DNA polymerase variants which are associated with cancer predisposition and tumour development. DNA polymerases delta and epsilon replicate the bulk of chromosomal DNA, and the cancer-associated variants have defects that interfere with proofreading during replication. Most of their 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.