Resolvase

Resolvase is an enzyme that resolves Holliday junctions formed during homologous recombination. It belongs to a class of structure-selective nucleases that cleave DNA four-way intermediates, converting them into separate DNA duplexes and thereby completing recombination repair or meiosis.

Holliday junctions are four-way DNA structures that arise during recombination. Resolvases introduce incisions on opposite strands across the junction. The two cuts can be made in different orientations, producing crossover or non-crossover products. The cleavage pattern determines the genetic outcome of recombination.

In bacteria, the canonical resolvase is RuvC, which acts with RuvA and RuvB to promote junction migration and stabilization. Additional resolvases include RusA, a phage-encoded enzyme. In eukaryotes, GEN1 functions as a true Holliday-junction resolvase, while SLX1-SLX4 and MUS81-EME1 act as structure-selective nucleases that process recombination intermediates. Yen1 is the fungal/yeast ortholog of GEN1. The activities of these enzymes are often coordinated with other nucleases and helicases to ensure proper resolution and genome maintenance.

Resolvases contribute to genome integrity by completing DNA repair and enabling accurate chromosome segregation during meiosis. Defects or misregulation can lead to accumulation of recombination intermediates, genome instability, and sensitivity to DNA damage. Their activity is tightly regulated throughout the cell cycle and integrated with broader DNA repair pathways.