Cancer Research UK

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Julie Cooper : Telomere Biology

Goals

Previous and current research

Our research focuses on the composition and functions of telomeres, the DNA-protein complexes that form the ends of linear chromosomes. Telomeres maintain the stability of genomic DNA by preventing degradation and fusion of chromosome ends, and by ensuring that bona fide chromosome ends do not elicit the cell cycle arrest pathways that respond to damage-induced DNA breaks.Telomeres have become a particular focus of research on tumorigenesis (which is associated with genomic instability and telomerase activation) and aging (which is accompanied by a gradual decline in telomere length). However, the mechanisms underlying telomere function are not yet understood, and indeed the complete functional repertoire of telomeres remains to be defined.

Future projects

The diversity of phenotypes found in taz1- cells allows us to explore not only the mechanisms underlying telomere function but also the ways in which telomere functions change with cell cycle progression and changing conditions. We can also use Taz1, as well as information on the fully-sequenced fission yeast genome, to identify additional telomere proteins. Indeed, we have recently identified and begun characterisation of a protein called Est1 that is required for telomerase activity. Issues we are pursuing include: [1] the mechanisms by which Taz1 performs its many functions, [2] the cell cycle regulation of telomere function, and the role of telomere dysfunction in impeding cell cycle progression, [3] the role of telomeres in sexual differentiation and meiosis, and [4] the identities and roles of other telomere-associated proteins in fission yeast.

Selected Papers

Jain D, Hebden AK, Nakamura TM, Miller KM, Cooper JP. HAATI survivors replace canonical telomeres with blocks of generic heterochromatin. Nature. 2010;467(7312):223-7 (Abstract)
Rog O, Miller KM, Ferreira MG, Cooper JP. Sumoylation of RecQ helicase controls the fate of dysfunctional telomeres. Molecular Cell. 2009;33:559-569 (Abstract)
Tomita K, Cooper JP. The telomere bouquet controls the meiotic spindle. Cell. 2007;130:113-126 (Abstract)
Miller KM, Rog O, Cooper JP. Semi-conservative DNA replication through telomeres requires Taz1. Nature. 2006;440:824-828 (Abstract)
Ferreira MG, Cooper JP. Two modes of DNA double-strand break repair are reciprocally regulated through the fission yeast cell cycle. Genes & Dev. 2004;18:2249-2254 (Abstract)
Miller K, Cooper JP. The telomere protein Taz1 is required to prevent and repair genomic DNA breaks. Molecular Cell. 2003;11:303-313 (Abstract)