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dnaQ is the gene encoding the ε subunit of DNA polymerase III in Escherichia coli.[1] The ε subunit is one of three core protein in the DNA polymerase complex. It functions as a 3’→5’ DNA directed proofreading exonuclease that removes incorrectly incorporated bases during replication.[2] dnaQ may also be referred to as mutD.[3]
Biological Role
[edit]Missense mutations in the dnaQ gene lead to the induction of the SOS DNA repair mechanism. Mutating the essential amino acid in the catalytic center of the ε subunit leads to complete loss of function.[4]
Overexpression of the ε subunit decreases the incidence of mutations with exposure to UV, proving that the epsilon subunit has an essential function in DNA editing and preventing the initiation of SOS DNA repair.[5]
The ε subunit has also been proven to have some impact on the growth rate of E. coli. Silencing of the dnaQ gene is correlated to significantly reduced growth.[6]
Interactions
[edit]The ε subunit is stabilized by the θ subunit within the complete polymerase complex.[7]
The gene encodes two functional domains: the N-terminus of the gene product binds the θ subunit and carries out the exonuclease function and the C-terminus binds the α subunit responsible for polymerase activity.[8]
A Q-linker peptide of 22 residues has been identified that links the α subunit to the ε subunit, conferring flexibility that sets the α:ε complex apart from other more restricted multi-domain proofreading polymerases.[9][10]
There is interaction between the missense suppressor glycine tRNA encoded by the mutA gene that is correlated to significantly increased mutation rate in cells that express the gene. The uncharged MutA tRNA possesses complementarity to a region in the 5' end of the dnaQ mRNA. This allows it to act as an antisense mRNA that directs the degradation of the dnaQ transcript and thus, a lower abundance of the subunit and increased frequency of mutation.[11] More recently, it was suggested that the tRNA directs replacement of essential glutamate residues with glycine, leading to aberrant ε subunits and resulting in an increase in mutations. Studies with T4 bacteriophage and E. coli with defective dnaQ genes give evidence that the mutA tRNA may not have any effect on the transcription of the dnaQ gene but may affect the translation of the gene product.[12]
Related sequences
[edit]Sequences have been found in other organisms that encode gene products with a similar function to dnaQ:
In Mycobaterium tuberculosis, the gene dnaE1 encodes a polymerase and histidinol-phosphatase (PHP) domain that carries out the 3’→5’ exonuclease and proofreading function.[13]
TREX1 is the major 3'→5' exonuclease in humans. It is responsible for metabolizing both single stranded DNA (ssDNA) and double stranded DNA (dsDNA) with mismatched 3' ends and is directed by endogenous retroelements. [14] Initially, TREX1 was called DNase III because it showed sequence homology with dnaQ in E. coli and with eukaryotic DNA polymerase epsilon, and possesses biochemical characteristics that associate with the capability of DNA proofreading.[15]
References
[edit]- ^ Scheuermann, R.; Tam, S.; Burgers, P. M.; Lu, C.; Echols, H (1983). "Identification of the epsilon-subunit of Escherichia coli DNA polymerase III holoenzyme as the dnaQ gene product: a fidelity subunit for DNA replication". Proc Natl Acad Sci U S A. 80 (23): 7085–7089. PMID 6359162.
- ^ Scheuermann, R. H.; Echols, H. (1984). "A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme". Proc Natl Acad Sci U S A. 81 (24): 7747–7751. PMID 392229.
- ^ Kornberg, Arthur; Baker, Tania (2005). DNA Replication (2nd ed.). California: University Science Books. p. 499. ISBN 1-891389-44-0.
- ^ Gautam, Satyendra; Kalindindi, Raju; Humayan, M. Zafri (1 July 2012). "SOS induction and mutagenesis by dnaQ missense alleles in wild type cells". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 735 (1–2): 46–50. doi:10.1016/j.mrfmmm.2012.05.004.
- ^ Jonczyk, Piotr; Fijalkowska, Iwona; Ciesla, Zygmunt (December 1988). "Overproduction of the epsilon subunit of DNA polymerase III counteracts the SOS mutagenic response of Escherichia coli". Proc Natl Acad Sci U S A. 85 (23): 9124–9127.
- ^ Stefan, Alessandra; Regianni, Luca (10 July 2003). "Silencing of the gene coding for the ϵ subunit of DNA polymerase III slows down the growth rate of Escherichia coli populations". FEBS Letters. 546 (2–3): 295–299. doi:10.1016/S0014-5793(03)00604-5.
- ^ Taft-Benz, Sharon A.; Schaaper, Roel M. (May 2004). "The θ Subunit of Escherichia coli DNA Polymerase III: a Role in Stabilizing the ε Proofreading Subunit". J. Bacteriol. 186 (9): 2774–2780. doi:10.1128/JB.186.9.2774-2780.2004.
- ^ Taft-Benz, Sharon A.; Schaaper, Roel M. (May 1999). "The C-Terminal Domain of DnaQ Contains the Polymerase Binding Site". J. Bacteriol. 181 (9): 2963–2695.
- ^ Ozawa, Kiyoshi; Jergic, Sobodan (28 July 2008). "The proofreading exonuclease subunit ε of Escherichia coli DNA polymerase III is tethered to the polymerase subunit α via a flexible linker". Nucl. Acids Res. 36 (15): 5074–5082. doi:10.1093/nar/gkn489.
- ^ Ozawa, Kiyoshi; Horan, Nicholas P. (10 April 2013). "Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits a , e , h and b reveals a highly flexible arrangement of the proofreading domain". Nuc. Acids Res. 41 (10): 5354–5367. doi:10.1093/nar/gkt162.
- ^ Dorazi, Robert (7 December 2003). "Can tRNAs act as antisense RNA? The case of mutA and dnaQ". J Theor. Biol. 225 (3): 383–388. doi:10.1016/S0022-5193(03)00268-6.
- ^ Al Mamun, Abu Amar M.; Gautam, Satyendra; Humayun, M. Zafri (1 November 2006). "Hypermutagenesis in mutA cells is mediated by mistranslational corruption of polymerase, and is accompanied by replication fork collapse". Mol. Micro. 62 (6): 1752–1763. doi:10.1111/j.1365-2958.2006.05490.x.
- ^ Du Toit, Andrea (6 May 2015). "An ancient mycobacterial proofreader". Nature Reviews Microbiology. 13 (329). doi:10.1038/nrmicro3493.
- ^ The Unitprot Consortium. "TREX1 - Three-prime repair exonuclease 1". UniprotKB. Retrieved 9 November 2015.
- ^ Höss, Matthias; Robins, Peter (1999). "A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein". The EMBO Journal. 18 (13): 3868–3875. doi:10.1093/emboj/18.13.3868.