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Decatenation Assays and Topo II – Supercoiled pBR322 Provided by TopoGEN

Decatenation Assays and Topo II – Supercoiled pBR322 Provided by TopoGEN

A non-canonical function of topoisomerase II  in disentangling dysfunctional telomeres

Thomas Germe, Kyle Miller1 and  Julia Promisel Cooper

Telomere Biology Laboratory, Cancer Research, London, UK

The decatenation activity of topoisomerase II (Top2), which is widely conserved within the eukaryotic domain, is essential for chromosomal segregation in mitosis.  It is less clear, however, whether Top2 performs the same function uniformly across the whole genome, and whether all its functions rely on decatenation.  In the fission yeast, Schizosaccharomyces pombe, telomeres are bound by Taz1, which promotes smooth replication fork progression through the repetitive telomeric sequences.  Hence, replication forks stall at taz1D telomeres.  This leads to telomeric entanglements at low temperatures (p201C) that cause chromosomal segregation defects and loss of viability.  Here, we show that the appearance of entanglements, and the resulting cold sensitivity of taz1D cells, is suppressed by mutated alleles of Top2 that confer slower catalytic turnover. This suppression does not rely on the decatenation activity of Top2.  Rather, the enhanced presence of reaction intermediates in which Top2 is clamped around DNA, promotes the removal of telomeric entanglements in vivo, independently of catalytic cycle completion. We propose a model for how the clamped enzyme–DNA complex promotes proper chromosomal segregation.

The EMBO Journal (2009) 28, 2803–2811. doi:10.1038/
emboj.2009.223; Published online 13 August 2009
Subject Categories: genome stability & dynamics
Keywords: DNA replication; Schizosaccharomyces pombe;
telomeres; topoisomerase II

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