Branch migration is the process by which base pairs on homologous

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

strands are consecutively exchanged at a

Holliday junction A Holliday junction is a branched nucleic acid structure that contains four double-stranded arms joined. These arms may adopt one of several conformations depending on buffer salt concentrations and the sequence of nucleobases closest to the j ...

, moving the branch point up or down the DNA sequence. Branch migration is the second step of

genetic recombination Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryot ...

, following the exchange of two single strands of DNA between two homologous chromosomes. The process is random, and the branch point can be displaced in either direction on the strand, influencing the degree of which the genetic material is exchanged. Branch migration can also be seen in

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

and replication, when filling in gaps in the sequence. It can also be seen when a foreign piece of DNA invades the strand.

Mechanism

The mechanism for branch migration differs between

prokaryote A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...

s and

eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

Prokaryotes

The mechanism for prokaryotic branch migration has been studied many times in ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

''. In ''E. coli,'' the proteins RuvA and RuvB come together and form a complex that facilitates the process in a number of ways. RuvA is a tetramer and binds to the DNA at the Holliday junction when it is in the open X form. The protein binds in a way that the DNA entering/departing the junction is still free to rotate and slide through. RuvA has a domain with acidic

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

residues that interfere with the base pairs in the centre of the junction. This forces the base pairs apart so that they can re-anneal with base pairs on the homologous strands. In order for migration to occur, RuvA must be associated with RuvB and ATP. RuvB has the ability to

hydrolyze Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

ATP, driving the movement of the branch point. RuvB is a hexamer with

helicase Helicases are a class of enzymes that are vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic double helix, separating the two hybridized ...

activity, and also binds the DNA. As ATP is hydrolyzed, RuvB rotates the recombined strands while pulling them out of the junction, but does not separate the strands as helicase would. The final step in branch migration is called resolution and requires the protein RuvC. The protein is a dimer, and will bind to the Holliday junction when it takes on the stacked X form. The protein has

endonuclease In molecular biology, endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain (namely DNA or RNA). Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (with regard to sequence), while man ...

activity, and cleaves the strands at exactly the same time. The cleavage is symmetrical, and gives two recombined DNA molecules with single stranded breaks.

Eukaryotes

The eukaryotic mechanism is much more complex involving different and additional proteins, but follows the same general path. Rad54, a highly conserved eukaryotic protein, is reported to oligomerize on

s to promote branch migration.

Archaea

A helicase (designated Saci-0814) isolated from the thermophilic crenarchaeon ''Sulfolobus acidocaldarius'' dissociated DNA Holliday junction structures, and showed branch migration activity ''in vitro''. In a ''S. acidocaldarius'' strain deleted for Saci-0814, the homologous recombination frequency was reduced five-fold compared to the parental strain indicating that Saci-0814 is involved in homologous recombination ''in vivo''. Based on this evidence it appears that Saci-0814 is employed in homologous recombination in ''S. acidocaldarius'' and functions as a branch migration helicase. Homologous recombination appears to be an important adaptation in hyperthermophiles, such as ''S. acidocaldarius'', for efficiently repairing DNA damage. Helicase Saci-0814 is classified as an aLhr1 (archaeal long helicase related 1) under superfamily 2 helicases, and its homologs are conserved among the archaea.

Control

The rate of branch migration is dependent on the amount of

divalent In chemistry, the valence (US spelling) or valency (British spelling) of an atom is a measure of its combining capacity with other atoms when it forms chemical compounds or molecules. Valence is generally understood to be the number of chemica ...

ions, specifically magnesium ions (Mg²⁺), present during recombination. The ions determine which structure the Holliday junction will adopt, as they play a stabilizing role. When the ions are absent, the backbones repel each other and the junction takes on the open X structure. In this condition, migration is optimal and the junction will be free to move up and down the strands. When the ions are present, they neutralize the negatively charged backbone. This allows the strands to move closer together and the junction adopts the stacked X structure. It is during this state that resolution will be optimal, allowing RuvC to bind to the junction.

References

{{reflist Cellular processes Molecular genetics