Hollidayjunction

A Holliday junction is a four-way, X-shaped DNA structure that forms during homologous recombination and certain DNA repair processes. Named after Robin Holliday, who proposed the model in 1964, the junction arises when strands from homologous DNA duplexes pair and exchange partners, creating a cross-shaped intermediate that can migrate along the DNA as the exchanged region expands.

Structure and formation: The Holliday junction consists of two double-stranded DNA duplexes held together by crossing strands at the junction. It often forms after a single-stranded nick or double-strand break initiates strand invasion and annealing with a homologous sequence, followed by capture of the second end. Branch migration can extend the region of heteroduplex DNA, and the junction can slide along the DNA until resolved.

Resolution and outcomes: Resolution of a Holliday junction is carried out by structure-specific nucleases called resolvases. The orientation of the cuts determines the outcome: cleavage on certain strands yields crossover products, where flanking genetic material is exchanged between chromosomes, while cleavage on the alternate strands yields non-crossover products, with no exchange of flanking markers. Some pathways, such as synthesis-directed strand annealing, can repair breaks without leaving a persistent Holliday junction.

Biological significance: Holliday junctions play a central role in meiosis, contributing to genetic diversity through crossovers. They are also involved in mitotic DNA repair. In bacteria, resolvases like RuvC resolve Holliday junctions, whereas in eukaryotes, related enzymes such as GEN1 and the SLX1-SLX4 and MUS81-EME1 complexes perform analogous functions.

Related concepts: The double Holliday junction model describes a prolonged junction formed during recombination, while alternative pathways like the synthesis-dependent strand-annealing model avoid stable junctions.