The X philes: structure-specific endonucleases that resolve Holliday junctions

Genetic recombination is a critical cellular process that promotes evolutio nary diversity, facilitates DNA repair and underpins genome duplication. It entails the reciprocal exchange of single strands between homologous DNA d uplexes to form a four-way branched intermediate commonly referred to as th e Holliday junction. BRA molecules interlinked in this way have to be separ ated in order to allow normal chromosome transmission at cell division, Thi s resolution reaction is mediated by structure-specific endonucleases that catalyse dual-strand incision across the point of strand cross-over. Hollid ay junctions can also arise at stalled replication forks by reversing the d irection of fork progression and annealing of nascent strands. Resolution o f junctions in this instance generates a DNA break and thus serves to initi ate rather than terminate recombination, Junction resolvases are generally small, homodimeric endonucleases with a high specificity for branched DNA, They use a metal-binding pocket to co-ordinate an activated water molecule for phosphodiester bond hydrolysis, In addition, most junction endonuclease s modulate the structure of the junction upon binding, and some display a p reference! for cleavage at specific nucleotide target sequences. Holliday j unction resolvases with distinct properties have been characterized from ba cteriophages (T4 endo VII, T7 endo I, RusA and Rap), Bacteria (RuvC), Archa ea (Hjc and Hje), yeast (CCE1) and poxviruses (A22R). Recent studies have b rought about a reappraisal of the origins of junction-specific endonuclease s with the discovery that RuvC, CCE1 and A22R share a common catalytic core .