Global InformationHomologous recombination information
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be also RNA in viruses).
Homologous recombination is widely used by cells to accurately repair harmful DNA breaks that occur on both strands of DNA, known as double-strand breaks (DSB), in a process called homologous recombinational repair (HRR).[1]
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.[2]
Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species of bacteria and viruses. Horizontal gene transfer is the primary mechanism for the spread of antibiotic resistance in bacteria.
Although homologous recombination varies widely among different organisms and cell types, for double-stranded DNA (dsDNA) 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, the further sequence of events may follow either of two main pathways discussed below (see Models); the DSBR (double-strand break repair) pathway or the SDSA (synthesis-dependent strand annealing) pathway. 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 DNA and RNA 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 homologous recombination 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; Capecchi[3] and Smithies[4] independently discovered applications to mouse embryonic stem cells, however the highly conserved mechanisms underlying the DSB repair model, including uniform homologous integration of transformed DNA (gene therapy), were first shown in plasmid experiments by Orr-Weaver, Szostak and Rothstein.[5][6][7] Researching the plasmid-induced DSB, using γ-irradiation[8] in the 1970s-1980s, led to later experiments using endonucleases (e.g. I-SceI) to cut chromosomes for genetic engineering of mammalian cells, where nonhomologous recombination is more frequent than in yeast.[9]
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- ^ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P, et al. (2002). "Chapter 5: DNA Replication, Repair, and Recombination". Molecular Biology of the Cell (4th ed.). New York: Garland Science. p. 845. ISBN 978-0-8153-3218-3. OCLC 145080076.
- ^ Capecchi MR (June 1989). "Altering the genome by homologous recombination". Science. 244 (4910): 1288–92. Bibcode:1989Sci...244.1288C. doi:10.1126/science.2660260. PMID 2660260.
- ^ Smithies O, Gregg RG, Boggs SS, Koralewski MA, Kucherlapati RS (1985-09-19). "Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination". Nature. 317 (6034): 230–4. Bibcode:1985Natur.317..230S. doi:10.1038/317230a0. PMID 2995814. S2CID 30212766.
- ^ Orr-Weaver TL, Szostak JW, Rothstein RJ (October 1981). "Yeast transformation: a model system for the study of recombination". Proceedings of the National Academy of Sciences of the United States of America. 78 (10): 6354–8. Bibcode:1981PNAS...78.6354O. doi:10.1073/pnas.78.10.6354. PMC 349037. PMID 6273866.
- ^ Orr-Weaver TL, Szostak JW (July 1983). "Yeast recombination: the association between double-strand gap repair and crossing-over". Proceedings of the National Academy of Sciences of the United States of America. 80 (14): 4417–21. Bibcode:1983PNAS...80.4417O. doi:10.1073/pnas.80.14.4417. PMC 384049. PMID 6308623.
- ^ Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW (May 1983). "The double-strand-break repair model for recombination". Cell. 33 (1): 25–35. doi:10.1016/0092-8674(83)90331-8. PMID 6380756. S2CID 39590123.
- ^ Resnick MA (June 1976). "The repair of double-strand breaks in DNA; a model involving recombination". Journal of Theoretical Biology. 59 (1): 97–106. Bibcode:1976JThBi..59...97R. doi:10.1016/s0022-5193(76)80025-2. PMID 940351.
- ^ Jasin M, Rothstein R (November 2013). "Repair of strand breaks by homologous recombination". Cold Spring Harbor Perspectives in Biology. 5 (11): a012740. doi:10.1101/cshperspect.a012740. PMC 3809576. PMID 24097900.