How homologous recombination is initiated: Unexpected evidence for single-strand nicks from V(D)J site-specific recombination

Views of how homologous recombination is initiated have changed over the past several decades: in the 1960s and 1970s, single-strand DNA lesions (nicks) were the leading contenders, but in the last decade, double-strand DNA breaks (DSBs) have reigned. In this issue of Cell, Lee et al. (2004) present evidence that nicks can stimulate homologous recombination and, in uncontrolled situations, may lead to translocations and other potentially dangerous genome rearrangements.