A Holliday junction is a junction between four strands of DNA. The structure is named after Robin Holliday, who proposed it in 1964 to account for a particular type of exchange of genetic information he observed in Ustilago maydis known as homologous recombination. Holliday junctions are highly conserved structures, from prokaryotes to mammals. Mobile Holliday junctions are an intermediate in genetic recombination which are also of importance in maintaining genomic integrity. In addition, cruciform structures involving Holliday junctions can arise to relieve helical strain in symmetrical sequences in DNA supercoils. Immobile Holliday junctions were artificially created by scientists at first to study their structure as a model for natural Holliday junctions, but they also later found use as basic structural building blocks in DNA nanotechnology.
Biological Holliday junctions are between homologous sequences, allowing them to slide up and down the DNA. In bacteria, this sliding (or branch migration) is facilitated by the RuvABC complex or RecG protein, molecular motors that use the energy of ATP hydrolysis to push the junction around. The junction must then be resolved, split up, to restore 2 linear duplexes. This can be done to either restore the parental configuration or to establish a crossed over configuration. Resolution can occur in either a horizontal or vertical fashion during homologous recombination, giving patch products (if in same orientation during double strand break repair) or splice products (if in different orientations during double strand break repair).
In prophase of meiosis I, duplicated homologous chromosomes pairs align end-to-end. Crossover can occur between aligned chromatids, leading to exchange of homologous segments by homologous recombination. This chromosome segregation through meiotic divisions leads to novel genotypes, first in gametes, then in offspring.
In the original Holliday model for homologous recombination, single-strand breaks occur at the same point on one strand of each parental DNA. Free ends of each broken strand then migrate across to the other DNA helix, where the invading strands are joined to the free ends they encounter. The resulting crossover junction is called a Holliday junction. As each crossover strand reanneals to its original partner strand it displaces the original complementary strand ahead of it, causing the Holliday junction to migrate. This creates heteroduplex DNA segments.
Cleavage and rejoining to re-establish two separate DNAs occurs in two ways: cleavage of the original broken strands, leading to two molecules that do not show crossover of markers in genes A and B; or cleavage of the other set of two strands, causing both of the resulting recombinant molecules to show crossover of markers in genes A and B.[clarification needed] All products, regardless of cleavage, are heteroduplexes in the region of Holliday junction migration.
In some cases, there is instead a double strand breakage. In this case, the 3' end is degraded and the longer 5' end invades the contiguous sister chromatid, forming a replication bubble. As this bubble nears the broken DNA, the longer 5' antisense strand again invades the sense strand of this portion of DNA, transcribing a second copy. When replication ends, both tails are reconnected to form two Holliday Junctions, which are then cleaved in a variety of patterns by proteins. An animation of this process can be seen here.
- Stahl FW (1 October 1994). "The Holliday junction on its thirtieth anniversary" (PDF). Genetics 138 (2): 241–246. PMC 1206142. PMID 7828807.
- Liu Y, West S (2004). "Happy Hollidays: 40th anniversary of the Holliday junction". Nat Rev Mol Cell Biol 5 (11): 937–44. doi:10.1038/nrm1502. PMID 15520813.
- Hays FA, Watson J, Ho PS (2003). "Caution! DNA Crossing: Crystal Structures of Holliday Junctions". J Biol Chem 278 (50): 49663–49666. doi:10.1074/jbc.R300033200. PMID 14563836.
- Constantinou A, Davies AA, West SC (2001). "Branch migration and Holliday junction resolution catalyzed by activities from mammalian cells". CELL 104 (2): 259–268. doi:10.1016/S0092-8674(01)00210-0. PMID 11207366.
- Fu TJ, Tse-Dinh YC, Seeman NC (1994). "Holliday junction crossover topology". J. Mol. Biol. 236 (1): 91–105. doi:10.1006/jmbi.1994.1121. PMID 8107128.
- Bloomfield, Victor A.; Crothers, Donald M.; Tinoco, Jr., Ignacio (2000). Nucleic acids: structures, properties, and functions. Sausalito, California: University Science Books. p. 468. ISBN 0935702490.
- Hartel, Daniel L.; Ruvolo, Maryellen (2012). Genetics: Analysis of Genetics and Genomes. Burlington: Jones & Bartlett.
- Helleday, T. "Double-Strand Break Repair via Double Holliday Junctions (Szostak Model)". Animation. MIT.
- Holliday junctions at the US National Library of Medicine Medical Subject Headings (MeSH)
- Conformational Change of Holliday Junction
- Analysis of branch migration activities of proteins using synthetic DNA substrates (a protocol)