Homologous Recombination

Homologous recombination is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. It is most widely used by cells to accurately repair harmful breaks that occur on both strands of DNA, known as double-strand breaks. Homologous recombination also produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and egg cells in animals. These new combinations of DNA represent genetic variation in offspring, which in turn enables populations to adapt during the course of evolution. Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species of bacteria and viruses.

Although homologous recombination varies widely among different organisms and cell types, most forms involve the same basic steps. After a double-strand break occurs, sections of DNA around the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule then "invades" a similar or identical DNA molecule that is not broken. After strand invasion, one or two cross-shaped structures called Holliday junctions connect the two DNA molecules. Depending on how the two junctions are cut by enzymes, the type of homologous recombination that occurs in meiosis results in either chromosomal crossover or non-crossover. Homologous recombination that occurs during DNA repair tends to result in non-crossover products, in effect restoring the damaged DNA molecule as it existed before the double-strand break.

Homologous recombination is conserved across all three domains of life as well as viruses, suggesting that it is a nearly universal biological mechanism. The discovery of genes for homologous recombination in protists—a diverse group of eukaryotic microorganisms—has been interpreted as evidence that meiosis emerged early in the evolution of eukaryotes. Since their dysfunction has been strongly associated with increased susceptibility to several types of cancer, the proteins that facilitate homologous recombination are topics of active research. Homologous recombination is also used in gene targeting, a technique for introducing genetic changes into target organisms. For their development of this technique, Mario Capecchi, Martin Evans and Oliver Smithies were awarded the 2007 Nobel Prize for Physiology or Medicine.

Read more about Homologous RecombinationHistory and Discovery, In Eukaryotes, In Bacteria, In Viruses, Effects of Dysfunction, Evolutionary Origins

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Homologous Recombination - Technological Applications - Cancer Therapy
... Cancer cells with BRCA mutations have deficiencies in homologous recombination, and drugs to exploit those deficiencies have been developed and used successfully in ... BRCA1 and BRCA2 are necessary for DNA repair by homologous recombination ... called base-excision repair usually compensates for the lack of DNA repair by homologous recombination ...
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... techniques of proper gene insertion is homologous recombination ... While homologous recombination avoids the problem of insertional mutagenesis, it is very inefficient, producing only about one out of a million cells that have actually taken up the new gene sequence ...
DNA Repair Mechanisms - Double-strand Breaks
... Three mechanisms exist to repair double-strand breaks (DSBs) non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination ... accurate repair, NHEJ relies on short homologous sequences called microhomologies present on the single-stranded tails of the DNA ends to be joined ... its DNA, since there is no template available for repair by homologous recombination ...