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Somatic recombination

Summary

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 edit

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]

References edit

  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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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