Recombinase

Recombinases are genetic recombination enzymes.

Site specific recombinases

Further information: Site-specific recombinase technology

DNA recombinases are widely used in multicellular organisms to manipulate the structure of genomes, and to control gene expression. These enzymes, derived from bacteria (bacteriophages) and fungi, catalyze directionally sensitive DNA exchange reactions between short (30–40 nucleotides) target site sequences that are specific to each recombinase. These reactions enable four basic functional modules: excision/insertion, inversion, translocation and cassette exchange, which have been used individually or combined in a wide range of configurations to control gene expression.[1][2][3][4][5]

Types include:

Homologous recombination

Recombinases have a central role in homologous recombination in a wide range of organisms. Such recombinases have been described in archaea, bacteria, eukaryotes and viruses.

Archaea

The archaeon Sulfolobus solfataricus RadA recombinase catalyzes DNA pairing and strand exchange, central steps in recombinational repair.[6] The RadA recombinase has greater similarity to the eukaryotic Rad51 recombinase than to the bacterial RecA recombinase.[6]

Bacteria

RecA recombinase appears to be universally present in bacteria. RecA has multiple functions, all related to DNA repair. RecA has a central role in the repair of replication forks stalled by DNA damage and in the bacterial sexual process of natural genetic transformation.[7][8]

Eukaryotes

Eukaryotic Rad51 and its related family members are homologous to the archaeal RadA and bacterial RecA recombinases. Rad51 is highly conserved from yeast to humans. It has a key function in the recombinational repair of DNA damages, particularly double-strand damages such as double-strand breaks. In humans, over- or under-expression of Rad51 occurs in a wide variety of cancers.

During meiosis Rad51 interacts with another recombinase, Dmc1, to form a presynaptic filament that is an intermediate in homologous recombination.[9] Dmc1 function appears to be limited to meiotic recombination. Like Rad51, Dmc1 is homologous to bacterial RecA.

Viruses

Some DNA viruses encode a recombinase that facilitates homologous recombination. A well-studied example is the UvsX recombinase encoded by bacteriophage T4.[10] UvsX is homologous to bacterial RecA. UvsX, like RecA, can facilitate the assimilation of linear single-stranded DNA into an homologous DNA duplex to produce a D-loop.

References

  1. ^ Nern, A; Pfeiffer, BD; Svoboda, K; Rubin, GM (Aug 23, 2011). "Multiple new site-specific recombinases for use in manipulating animal genomes". Proceedings of the National Academy of Sciences of the United States of America. 108 (34): 14198–203. Bibcode:2011PNAS..10814198N. doi:10.1073/pnas.1111704108. PMC 3161616. PMID 21831835.
  2. ^ García-Otín, AL; Guillou, F (Jan 1, 2006). "Mammalian genome targeting using site-specific recombinases". Frontiers in Bioscience. 11: 1108–36. doi:10.2741/1867. PMID 16146801.
  3. ^ Dymecki, SM; Kim, JC (Apr 5, 2007). "Molecular neuroanatomy's "Three Gs": a primer". Neuron. 54 (1): 17–34. doi:10.1016/j.neuron.2007.03.009. PMC 2897592. PMID 17408575.
  4. ^ Luan, H; White, BH (Oct 2007). "Combinatorial methods for refined neuronal gene targeting". Current Opinion in Neurobiology. 17 (5): 572–80. doi:10.1016/j.conb.2007.10.001. PMID 18024005. S2CID 36457021.
  5. ^ Fenno, LE; Mattis, J; Ramakrishnan, C; Hyun, M; Lee, SY; He, M; Tucciarone, J; Selimbeyoglu, A; Berndt, A; Grosenick, L; Zalocusky, KA; Bernstein, H; Swanson, H; Perry, C; Diester, I; Boyce, FM; Bass, CE; Neve, R; Huang, ZJ; Deisseroth, K (Jul 2014). "Targeting cells with single vectors using multiple-feature Boolean logic". Nature Methods. 11 (7): 763–72. doi:10.1038/nmeth.2996. PMC 4085277. PMID 24908100.
  6. ^ a b Seitz EM, Brockman JP, Sandler SJ, Clark AJ, Kowalczykowski SC (1998). "RadA protein is an archaeal RecA protein homolog that catalyzes DNA strand exchange". Genes Dev. 12 (9): 1248–53. doi:10.1101/gad.12.9.1248. PMC 316774. PMID 9573041.
  7. ^ Cox MM, Goodman MF, Kreuzer KN, Sherratt DJ, Sandler SJ, Marians KJ (2000). "The importance of repairing stalled replication forks". Nature. 404 (6773): 37–41. Bibcode:2000Natur.404...37C. doi:10.1038/35003501. PMID 10716434. S2CID 4427794.
  8. ^ Michod RE, Bernstein H, Nedelcu AM (2008). "Adaptive value of sex in microbial pathogens". Infect. Genet. Evol. 8 (3): 267–85. Bibcode:2008InfGE...8..267M. doi:10.1016/j.meegid.2008.01.002. PMID 18295550.
  9. ^ Crickard JB, Kaniecki K, Kwon Y, Sung P, Greene EC (2018). "Spontaneous self-segregation of Rad51 and Dmc1 DNA recombinases within mixed recombinase filaments". J. Biol. Chem. 293 (11): 4191–4200. doi:10.1074/jbc.RA117.001143. PMC 5858004. PMID 29382724.
  10. ^ Bernstein C, Bernstein H (2001). DNA repair in bacteriophage. In: Nickoloff JA, Hoekstra MF (Eds.) DNA Damage and Repair, Vol.3. Advances from Phage to Humans. Humana Press, Totowa, NJ, pp. 1–19. ISBN 978-0896038035


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