The result of the crossing over event is known as recombination. It occurs mostly between the homologous chromosomes during the meiosis. The process of crossing over gives a few different alleles to the daughter chromosomes as compared to the parent chromosomes. There are two main types of recombination such as homologous recombination and site-specific recombination. The generalized one is known as the homologous recombination. It occurs between the DNA segments having sequence homology. Site-specific recombination involves a specific one. It occurs between the segments with short sequence homology.
Homologous recombination:
Image 1: Holliday model for recombination
Two key features of homologous recombination include breakage-reunion of the polynucleotides, and enzymes or proteins mediated regulation. Many of the findings led to the discovery of processes involved in homologous recombination. One of the important findings by Robin Holliday and Matthew Meselson paved a way. It is known as the Holliday model of recombination.
The Holliday model explains the process of recombination between two homologous double-stranded molecules. They may have identical or nearly identical sequences. The recombination pattern mostly involves a double-stranded DNA. The first step occurring in homologous recombination involves a single-stranded nick appearing at each helix. The single-stranded ends with the nicks get involved in the exchange. The process involves a base pairing between the exchanged strands and the intact strand. Base pairing leads to sequence similarity and stabilizes the structure formed due to the base pairing. This structure is known as a heteroduplex. The second step involves the sealing of the gaps generated during the process of exchange. An enzyme known as DNA ligase helps in sealing the gaps. The resulting structure is known as the Holliday structure. It is a dynamic structure and leads to branch migration.
The longer DNA segments in the structure get exchanged after the branch migration. After this, the branch point gets cleaved. The cleavage across the branch point leads to an important event. It brings back the resolution of the structure to its original form. It is known as the chi form. It involves the cuts made in either of the orientation. There are two key types of cuts targeting the chi form. One type of cut starts from the left and cleaves towards the right (Left-Right). The other type of cut starts from the above and goes on cleaving while traveling downwards (up-down). The left-right cut gives rise to the horizontal resolution. The up-down cut gives rise to reciprocal strand exchange or vertical resolution. The left-right cut gives rise to the transfer of a short segment of the polynucleotide. It corresponds to the distance migrated by the branch. In the reciprocal exchange, the double-stranded DNA gets transferred between the two molecules. End of one molecule exchanges with the end of the other molecule. It is a typical feature of crossing over.
Although Holliday model explained the recombination process in its best possible way, it got criticized for a single point. Nicks may not necessarily occur precisely in the same position. Hence, it was taken for remodification by Meselson and Radding. They explained their model known as Meselson-Radding Model of recombination. The first step involved a single-stranded nick in just one of the double-stranded DNA giving rise to a free end. The free end shows an ability to invade the unbroken double-stranded DNA. The invasion occurs at the homologous position. Hence, it displaces one of its strand forming a D-loop. Cleavage of the displaced strand at the junction between the single-stranded region and the base pair region gives rise to a heteroduplex.
Both the models proved inadequate in explaining the gene conversion process. It occurs commonly in the yeast and the fungal cells. Later on, another model known as the double-strand break model got approved. It explained the homologous recombination by covering the gene conversion process. In the yeast, two gametes fuse and form a zygote. It forms an ascus having four haploid spores with genotypes. Consider the fusion of gametes having a different set of alleles. The ascus consists of two different types of genotypes. Two ascospores show one genotype. The other two ascospores show the other genotype. Hence, they show 2:2 segregation pattern. Sometimes, the gene conversion shows 3:1 ratio. The ratio gets explained by one of the alleles. One of its types gets converted to the other type in a recombination event during meiosis.
The double-strand break model opposes the Meselson Radding modification by explaining the double-strand cut and not the single-strand cut. A double-strand break occurs in both the strands of a DNA. One strand gets shortened at each end leading to the 3’ overhangs. The exonuclease trims the cut strands. The next step involves strand invasion. One of the overhangs invades homologous DNA segment giving rise to Holliday junction. The strand extension after the process of migration occurs due to the activity of DNA polymerase enzyme. After the process of ligation, the heteroduplex formation involves two Holliday junctions. Later on, the Holliday junction gets cleaved. The findings of the double-strand break model revealed two important points. The first point mentioned about the double strand breaks occurring in the meiosis. The second finding revealed the role of homologous recombination in DNA repair.
Image 2: Double-strand break model
Site-specific recombination:
It usually occurs in the bacteriophages. These viruses infect the bacterial cells for replicating the progeny phages. Once it injects its genome into the bacterial cells, it follows two pathways such as lytic and the lysogenic pathways. The lytic cycle produces phage coat proteins and leads to phage genome replication. It releases the progeny phages by lysing the bacterial cells. The lysogenic cycle involves a different mechanism. The lambda phage genome stays in the bacterial cells for many cell divisions. The lambda genome exists in the quiescent form known as a prophage. The lambda genome gets integrated into the bacterial chromosome and replicates. The integration involves site-specific recombination. The process occurs between the two sites such as att P site of the lambda genome and the att B site of the bacterial chromosome. If the att site gets inactivated, the process of recombination occurs in some other site having sequence similarity.
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