Cell Press, Molecular Cell, 4(36), p. 539-540, 2009
DOI: 10.1016/j.molcel.2009.11.003
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DNA strand exchanges between homologous sequences promoted by RecA-like recombinases are essential for accurate repair of DNA double-strand breaks (DSBs) and maintenance of genome integrity. Canonical DSB repair models stipulate that the substrate used by recombinases to invade an intact homologous duplex DNA and generate a D loop after strand exchange is a tailed duplex with a protruding 3′ single-stranded extension. In vitro, however, recombinases can promote strand invasion using either a 3′- or a 5′-tailed duplex. In this issue of Molecular Cell, Mazloum and Holloman (2009b) found that the Ustilago maydis Rad51 recombinase exhibits more efficient strand invasion with a 5′- than with a 3′-tailed duplex. In addition, the fungal BRCA2 relative Brh2 significantly stimulated strand invasion with both a 5′- and a 3′-tailed duplex. The biological relevance of this robust and “unconventional” 5′-tailed duplex strand invasion has so far not been fully explored, most probably because of the prevalence of the 5′-to-3′ end resection observed at both mitotic and meiotic DSBs (Mimitou and Symington, 2009). Even though only 3′ end strand invasion is integrated in canonical DSB repair models, it is possible that 5′ end strand invasion could be involved in the repair of broken DNA replication forks.