Homologous recombination

Exchange or repair using corresponding DNA sequences as templates. It can restore a broken molecule and can yield crossover or noncrossover products; sequence repair and reshuffling of inherited alleles are compatible outcomes.

A Holliday junction is a four-way DNA branch in which strands exchange pairing partners between homologous duplexes. It can occur as an intermediate in homologous recombination. The molecular configuration is distinct from a final chromosomal crossover, which is classified by the exchange of flanking chromosome arms. Robin Holliday's 1964 model connected strand exchange, hybrid DNA and gene conversion.^[ref]

For a schematic example, label homologous regions by distant markers $L\cdots R$ and $l\cdots r$. Alternative strand-pair cleavage and rejoining routes at a junction can preserve the parental combinations $L\cdots R$, $l\cdots r$, or produce the exchanged combinations $L\cdots r$, $l\cdots R$. Local mismatches and their repair can change an allele independently of that distant-marker outcome. The historical diagram illustrates possibilities; it does not establish equal frequencies for these outcomes in every cell.^[ref]

Later work sought physical evidence. H. Potter and D. Dressler isolated colicinE1 plasmid DNA, linearized it with the restriction enzyme EcoRI, and examined it by electron microscopy. They found crossed structures containing two genome lengths, joined at homologous regions. Such forms occurred in wild-type and tested RecB-C hosts but were absent in their recombination-deficient RecA hosts. They interpreted these controlled observations as intermediates of the Holliday model.^[ref]

The combination of shape, DNA content and a genetic control is stronger evidence than an X-shaped image alone. A Holliday junction also need not be an obligatory step in every noncrossover recombination pathway; the outcome and the route producing it remain separate questions.

Branch migration is movement of the strand-exchange point in a Holliday junction. Successive changes in base pairing shift the junction along homologous DNA without requiring a new break in each phosphodiester backbone. Moving the boundary changes the extent of heteroduplex DNA, where strands from different parental DNA molecules pair together.

An illuminating experiment built two double-stranded DNA substrates with complementary single-stranded tails. Pairing the tails formed a four-stranded junction at one end. Complete branch migration to the opposite end produced two strand-exchanged duplex products, giving an observable endpoint for a process otherwise occurring along a molecular junction.^[ref]

The spontaneous reaction depended strongly on the surrounding ions: under the reported conditions, removing magnesium made it roughly a thousand times faster. This is not a universal speed for DNA exchange inside a cell; the experiment isolated a spontaneous process whose kinetics depend on junction structure and solution conditions.^[ref]

Noncrossover recombination is an outcome of homologous recombination without reciprocal exchange of the chromosome arms flanking the repaired region. Homologous sequence can provide a template for repair, and local sequence information can change, even though the flanking-marker arrangement remains parental. Absence of a chromosomal crossover therefore does not imply absence of recombination.^[ref]

For a schematic example, write one DNA region as $LCR$ and its homolog as $lcr$, where the outer letters are distinguishable flanking markers. Repair of the first molecule can copy a short tract containing $c$ and produce $LcR$, while retaining its original $L$–$R$ flanking combination. This is compatible with local gene conversion and a noncrossover outcome. A crossover exchanging the right-hand arms would instead alter the linkage of those distant markers.

A yeast study distinguished the outcomes experimentally by following DNA intermediates and products through meiosis. Noncrossover heteroduplex products appeared earlier than crossovers. In a mutant that accumulated unresolved Holliday junction intermediates and formed very few crossovers, noncrossover products still appeared with normal timing and abundance. The findings argued against treating all noncrossovers as merely the alternative late resolution of one common junction intermediate.^[ref]

The term classifies the final relationship of flanking sequences. It does not specify one universal repair pathway, and observing an unchanged pair of distant markers alone may miss local sequence changes.

Meiotic recombination is homologous recombination occurring during meiosis. It can exchange segments between homologous chromosomes through crossing over, while noncrossover recombination repairs or changes local sequence without reciprocal exchange of the chromosome arms. These outcomes connect the repair of DNA with reshuffling of inherited alleles.

In budding yeast, a decisive experiment purified DNA ends carrying a covalently attached protein from mutants that accumulated meiotic DNA double-strand breaks. The attached protein was identified as Spo11, strongly implicating it in catalysing the initiating cleavage rather than merely responding after accidental damage.^[ref]

For an illustrative two-marker example, suppose the replicated homologues carry AB and ab. A single reciprocal exchange between the genetic markers, involving one chromatid from each homologue, can leave four chromatids carrying AB, Ab, aB and ab. Two are recombinant for those markers and two retain the parental combinations. More generally, the relation between observed marker combinations and physical exchanges depends on the positions and number of exchanges.

Recombination between related chromosomes derived from different ancestral genomes, distinguished from recombination between true homologues.