Somatic recombination

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Somatic recombination, as opposed to the genetic recombination that occurs in meiosis, is an alteration of the DNA of a somatic cell that is inherited by its daughter cells. The term is usually reserved for large-scale alterations of DNA such as chromosomal translocations and deletions and not applied to point mutations. Somatic recombination occurs physiologically in the assembly of the B cell receptor and T-cell receptor genes (V(D)J recombination), [1] as well as in the class switching of immunoglobulins. [2] Somatic recombination is also important in the process of carcinogenesis. [3]

In neurons of the human brain, somatic recombination occurs in the gene that encodes the amyloid precursor protein APP. [4] Neurons from individuals with sporadic Alzheimer's disease show greater APP gene diversity due to somatic recombination than neurons from healthy individuals. [4]

Plants

Intrachromosomal homologous recombination in Arabidopsis thaliana plants was found to occur in all organs examined from the seed stage to the flowering stage of somatic plant development. [5] Recombination frequencies were typically in the range of 10−6 to 10−7 events per genome. [5] A. thaliana mutants selected for hypersensitivity to X-irradiation also proved to be simultaneously hypersensitive to the DNA damaging agents mitomycin C and/or methyl methanesulfonate. [6] The mutants were also deficient in somatic homologous recombination. [6] These findings suggest that repair of some types of DNA damage requires a recombinational process that was defective in the mutants studied. In nature, plants are continuously exposed to UV-B (280-320 nm) radiation, a component of sunlight that damages the DNA of somatic cells. [7] Cyclobutane pyrimidine dimers (CPD) are a type of damage induced by UV-B. In A. thaliana, homologous recombination appears to be directly involved in repairing CPD damage. [7]

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<i>Arabidopsis thaliana</i> Model plant species in the family Brassicaceae

Arabidopsis thaliana, the thale cress, mouse-ear cress or arabidopsis, is a small plant from the mustard family (Brassicaceae), native to Eurasia and Africa. Commonly found along the shoulders of roads and in disturbed land, it is generally considered a weed.

<span class="mw-page-title-main">Genetic recombination</span> Production of offspring with combinations of traits that differ from those found in either parent

Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.

<span class="mw-page-title-main">Mosaic (genetics)</span> Condition in multi-cellular organisms

Mosaicism or genetic mosaicism is a condition in which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Mosaicism is one of several possible causes of chimerism, wherein a single organism is composed of cells with more than one distinct genotype.

RecQ helicase is a family of helicase enzymes initially found in Escherichia coli that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H2O → NDP + P to drive the unwinding of either DNA or RNA.

<span class="mw-page-title-main">Cryptochrome</span> Class of photoreceptors in plants and animals

Cryptochromes are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name cryptochrome was proposed as a portmanteau combining the chromatic nature of the photoreceptor, and the cryptogamic organisms on which many blue-light studies were carried out.

<span class="mw-page-title-main">Mitomycins</span> Group of antibiotics

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<span class="mw-page-title-main">Photolyase</span> Class of enzymes

Photolyases are DNA repair enzymes that repair damage caused by exposure to ultraviolet light. These enzymes require visible light both for their own activation and for the actual DNA repair. The DNA repair mechanism involving photolyases is called photoreactivation. They mainly convert pyrimidine dimers into a normal pair of pyrimidine bases. Photo reactivation, the first DNA repair mechanism to be discovered, was described initially by Albert Kelner in 1949 and independently by Renato Delbecco also in 1949.

A meiocyte is a type of cell that differentiates into a gamete through the process of meiosis. Through meiosis, the diploid meiocyte divides into four genetically different haploid gametes. The control of the meiocyte through the meiotic cell cycle varies between different groups of organisms.

Mitotic recombination is a type of genetic recombination that may occur in somatic cells during their preparation for mitosis in both sexual and asexual organisms. In asexual organisms, the study of mitotic recombination is one way to understand genetic linkage because it is the only source of recombination within an individual. Additionally, mitotic recombination can result in the expression of recessive alleles in an otherwise heterozygous individual. This expression has important implications for the study of tumorigenesis and lethal recessive alleles. Mitotic homologous recombination occurs mainly between sister chromatids subsequent to replication. Inter-sister homologous recombination is ordinarily genetically silent. During mitosis the incidence of recombination between non-sister homologous chromatids is only about 1% of that between sister chromatids.

<span class="mw-page-title-main">Ku (protein)</span>

Ku is a dimeric protein complex that binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Ku is evolutionarily conserved from bacteria to humans. The ancestral bacterial Ku is a homodimer. Eukaryotic Ku is a heterodimer of two polypeptides, Ku70 (XRCC6) and Ku80 (XRCC5), so named because the molecular weight of the human Ku proteins is around 70 kDa and 80 kDa. The two Ku subunits form a basket-shaped structure that threads onto the DNA end. Once bound, Ku can slide down the DNA strand, allowing more Ku molecules to thread onto the end. In higher eukaryotes, Ku forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK. Ku is thought to function as a molecular scaffold to which other proteins involved in NHEJ can bind, orienting the double-strand break for ligation.

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Gene targeting is a biotechnological tool used to change the DNA sequence of an organism. It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombination. Gene targeting can be used to make a range of sizes of DNA edits, from larger DNA edits such as inserting entire new genes into an organism, through to much smaller changes to the existing DNA such as a single base-pair change. Gene targeting relies on the presence of a repair template to introduce the user-defined edits to the DNA. The user will design the repair template to contain the desired edit, flanked by DNA sequence corresponding (homologous) to the region of DNA that the user wants to edit; hence the edit is targeted to a particular genomic region. In this way Gene Targeting is distinct from natural homology-directed repair, during which the ‘natural’ DNA repair template of the sister chromatid is used to repair broken DNA. The alteration of DNA sequence in an organism can be useful in both a research context – for example to understand the biological role of a gene – and in biotechnology, for example to alter the traits of an organism.

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References

  1. ↑ Gellert M (1992). "Molecular analysis of V(D)J recombination". Annu Rev Genet. 26: 425–46. doi:10.1146/annurev.ge.26.120192.002233. PMID   1482120.
  2. ↑ Hein K, Lorenz MG, Siebenkotten G, et al. (1998). "Processing of switch transcripts is required for targeting of antibody class switch recombination". J Exp Med. 188 (12): 2369–74. doi:10.1084/jem.188.12.2369. PMC   2212419 . PMID   9858523.
  3. ↑ Ramel C, Cederberg H, Magnusson J, et al. (1996). "Somatic recombination, gene amplification and cancer". Mutat Res. 353 (1–2): 85–107. doi:10.1016/0027-5107(95)00243-x. PMID   8692194.
  4. 1 2 Lee MH, Siddoway B, Kaeser GE, Segota I, Rivera R, Romanow WJ, Liu CS, Park C, Kennedy G, Long T, Chun J (November 2018). "Somatic APP gene recombination in Alzheimer's disease and normal neurons". Nature. 563 (7733): 639–645. Bibcode:2018Natur.563..639L. doi:10.1038/s41586-018-0718-6. PMC   6391999 . PMID   30464338.
  5. 1 2 Swoboda P, Gal S, Hohn B, Puchta H. Intrachromosomal homologous recombination in whole plants. EMBO J. 1994 Jan 15;13(2):484-9. doi: 10.1002/j.1460-2075.1994.tb06283.x. PMID 8313893; PMCID: PMC394832
  6. 1 2 Masson JE, Paszkowski J. Arabidopsis thaliana mutants altered in homologous recombination. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11731-5. doi: 10.1073/pnas.94.21.11731. PMID 9326679; PMCID: PMC23619
  7. 1 2 Ries G, Buchholz G, Frohnmeyer H, Hohn B. UV-damage-mediated induction of homologous recombination in Arabidopsis is dependent on photosynthetically active radiation. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13425-9. doi: 10.1073/pnas.230251897. PMID 11069284; PMCID: PMC27240


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