Chromosomal crossover

Homologous Recombination is the process by which two chromosomes, paired up during prophase 1 of meiosis, exchange some distal portion of their DNA. Crossover occurs when two chromosomes, normally two homologous instances of the same chromosome, break and then reconnect but to the different end piece. If they break at the same place or locus in the sequence of base pairs, the result is an exchange of genes, called genetic recombination. This outcome is the normal way for crossover to occur. If they break at slightly different loci, the result can be a duplication of genes on one chromosome and a deletion of these on the other. This is known as an unequal crossover. If chromosomes break and rejoin on opposite sides of the centromere, the result can be one chromosome being lost during cell division. Any pair of homologous chromosomes may be expected to cross over multiple times during meiosis, depending on the species and length of the chromosome. The recombination is activily assisted in the cell by machinery that has been well conserved through evolution. This reduces the genetic linkage between genes on the same chromosome. The genetic variation of a population is thereby increased through chromosomal crossover. Independent assortment is a somewhat related process operating on the complete set of chromosomes. Crossing over was first described by Thomas Hunt Morgan, and the physical basis of crossing over was first demonstrated by Harriet Creighton and Barbara McClintock in 1931.

The production of knockout mice, for example, uses this machinery to incorporate altered DNA sequences into the genome.

The basis for this is double strand break (DSB) repair. DSB repair encompasses the related pathways of:
 * Non-Homologous End Joining (NHEJ)
 * Synthesis-Dependent Strand Annealing (SDSA)
 * Break Induced Replication (BIR)
 * Singel Strand Annealing (SSA)

Depending on topology requirements, these mechanisms may or may not involve a Holliday junction (HJ).