Recombinase
Genetic recombination enzymes
Recombinases are genetic recombination enzymes .
Site specific recombinases
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
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- 1 2 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 .
- ↑ 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 .
- ↑ Michod RE, Bernstein H, Nedelcu AM (2008). "Adaptive value of sex in microbial pathogens". Infect. Genet. Evol . 8 (3): 267–85. doi : 10.1016/j.meegid.2008.01.002 . PMID 18295550 .
- ↑ 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 .
- ↑ 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
External links
- Recombinases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)