View source for DnaQ

{{lowercase|title=dnaQ}}
{{Infobox nonhuman protein
| Name = DNA pol III epsilon subunit
| image = PDB 2gui EBI.jpg
| width = 
| caption = {{PDB|2GUI}}
| Organism = ''[[Escherichia coli]]''<br/>(str. K-12 substr. MG1655)
| TaxID = 511145
| Symbol = dnaQ
| AltSymbols = 
| EntrezGene = 946441
| PDB = 
| RefSeqmRNA = 
| RefSeqProtein = NP_414751.1
| UniProt = P03007
| ECnumber = 2.7.7.7
| Chromosome = genome
| EntrezChromosome = NC_000913.2
| GenLoc_start = 235956
| GenLoc_end = 236907
}}
'''''dnaQ''''' is the gene encoding the ε subunit of [[DNA polymerase III]] in ''[[Escherichia coli]]''.<ref>{{cite journal | vauthors = Scheuermann R, Tam S, Burgers PM, Lu C, Echols H | title = Identification of the epsilon-subunit of Escherichia coli DNA polymerase III holoenzyme as the dnaQ gene product: a fidelity subunit for DNA replication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 23 | pages = 7085–9 | date = December 1983 | pmid = 6359162 | pmc = 389997 | doi = 10.1073/pnas.80.23.7085 | doi-access = free }}</ref> The ε subunit is one of three core proteins in the DNA polymerase complex. It functions as a 3’→5’ DNA directed [[Proofreading (biology)|proofreading]] [[exonuclease]] that removes incorrectly incorporated bases during replication.<ref>{{cite journal | vauthors = Scheuermann RH, Echols H | title = A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 24 | pages = 7747–51 | date = December 1984 | pmid = 6393125 | pmc = 392229 | doi = 10.1073/pnas.81.24.7747 | doi-access = free }}</ref> ''dnaQ'' may also be referred to as ''mutD''.<ref>{{cite book | last1 = Kornberg | first1 = Arthur | last2 = Baker | first2 = Tania | name-list-style = vanc | title=DNA Replication|date=2005|publisher=University Science Books|location=California|isbn=1-891389-44-0|page=499|edition=2nd}}</ref>

==Biological role==

Missense mutations in the ''dnaQ'' gene lead to the induction of the [[SOS response|SOS DNA repair]] mechanism. Mutating the essential amino acid in the catalytic center of the ε subunit leads to complete loss of function.<ref>{{cite journal | vauthors = Gautam S, Kalidindi R, Humayun MZ | title = SOS induction and mutagenesis by dnaQ missense alleles in wild type cells | journal = Mutation Research | volume = 735 | issue = 1–2 | pages = 46–50 | date = July 2012 | pmid = 22677460 | doi = 10.1016/j.mrfmmm.2012.05.004 | pmc = 3389301 }}</ref>

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.<ref>{{cite journal | vauthors = Jonczyk P, Fijalkowska I, Ciesla Z | title = Overproduction of the epsilon subunit of DNA polymerase III counteracts the SOS mutagenic response of Escherichia coli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 23 | pages = 9124–7 | date = December 1988 | pmid = 3057500 | pmc = 282676 | doi = 10.1073/pnas.85.23.9124 | doi-access = free }}</ref>

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.<ref>{{cite journal | vauthors = Stefan A, Reggiani L, Cianchetta S, Radeghieri A, Gonzalez Vara y Rodriguez A, Hochkoeppler A | title = Silencing of the gene coding for the epsilon subunit of DNA polymerase III slows down the growth rate of Escherichia coli populations | journal = FEBS Letters | volume = 546 | issue = 2–3 | pages = 295–9 | date = July 2003 | pmid = 12832057 | doi = 10.1016/S0014-5793(03)00604-5 | doi-access =  }}</ref>

== Interactions ==

The ε subunit is stabilized by the θ subunit within the complete polymerase complex.<ref>{{cite journal | vauthors = Taft-Benz SA, Schaaper RM | title = The theta subunit of Escherichia coli DNA polymerase III: a role in stabilizing the epsilon proofreading subunit | journal = Journal of Bacteriology | volume = 186 | issue = 9 | pages = 2774–80 | date = May 2004 | pmid = 15090519 | doi = 10.1128/JB.186.9.2774-2780.2004 | pmc = 387820 }}</ref>

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.<ref>{{cite journal | vauthors = Taft-Benz SA, Schaaper RM | title = The C-terminal domain of dnaQ contains the polymerase binding site | journal = Journal of Bacteriology | volume = 181 | issue = 9 | pages = 2963–5 | date = May 1999 | doi = 10.1128/JB.181.9.2963-2965.1999 | pmid = 10217794 | pmc=93745}}</ref>

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.<ref>{{cite journal | vauthors = Ozawa K, Jergic S, Park AY, Dixon NE, Otting G | title = The proofreading exonuclease subunit epsilon of Escherichia coli DNA polymerase III is tethered to the polymerase subunit alpha via a flexible linker | journal = Nucleic Acids Research | volume = 36 | issue = 15 | pages = 5074–82 | date = September 2008 | pmid = 18663010 | doi = 10.1093/nar/gkn489 | pmc = 2528190 }}</ref><ref>{{cite journal | vauthors = Ozawa K, Horan NP, Robinson A, Yagi H, Hill FR, Jergic S, Xu ZQ, Loscha KV, Li N, Tehei M, Oakley AJ, Otting G, Huber T, Dixon NE | title = Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits α, epsilon, θ and β reveals a highly flexible arrangement of the proofreading domain | journal = Nucleic Acids Research | volume = 41 | issue = 10 | pages = 5354–67 | date = May 2013 | pmid = 23580545 | doi = 10.1093/nar/gkt162 | pmc = 3664792 }}</ref>

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.<ref>{{cite journal|last1=Dorazi|first1=Robert|title=Can tRNAs act as antisense RNA? The case of mutA and dnaQ|journal=J. Theor. Biol.|date=7 December 2003|volume=225|issue=3|pages=383–388|doi=10.1016/S0022-5193(03)00268-6|pmid=14604591}}</ref> 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.<ref>{{cite journal|last1=Al Mamun|first1=Abu Amar M.|last2=Gautam|first2=Satyendra|last3=Humayun|first3=M. Zafri|title=Hypermutagenesis in mutA cells is mediated by mistranslational corruption of polymerase, and is accompanied by replication fork collapse|journal=Mol. Micro.|date=1 November 2006|volume=62|issue=6|pages=1752–1763|doi=10.1111/j.1365-2958.2006.05490.x|pmid=17427291|doi-access=free}}</ref>

==Related sequences==
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.<ref>{{cite journal|last1=Du Toit|first1=Andrea | name-list-style = vanc | title = An ancient mycobacterial proofreader|journal=Nature Reviews Microbiology|date=6 May 2015|volume=13|issue=329|page=329 |doi=10.1038/nrmicro3493 |s2cid=39285107 }}</ref>

''[[TREX1]]'', the major 3'→5' exonuclease in humans, was initially called DNase III because it showed sequence homology with ''dnaQ'' in E. coli and with eukaryotic [[DNA polymerase epsilon]] and to possess biochemical characteristics that associate with the capability of DNA proofreading.<ref>{{cite journal | vauthors = Höss M, Robins P, Naven TJ, Pappin DJ, Sgouros J, Lindahl T | title = A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein | journal = The EMBO Journal | volume = 18 | issue = 13 | pages = 3868–75 | date = July 1999 | pmid = 10393201 | pmc = 1171463 | doi = 10.1093/emboj/18.13.3868 }}</ref> 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]].<ref>{{cite web|last1=The Unitprot Consortium|title=TREX1 - Three-prime repair exonuclease 1|url=https://www.uniprot.org/uniprot/Q9NSU2|website=UniprotKB|access-date=9 November 2015}}</ref>

==Evolution of dnaQ==

During [[DNA replication]] in bacteria two key functions are expressed. The first is a DNA polymerizing function of [[DNA polymerase]], and the second is a 3’ to 5’ [[exonuclease]] editing function.  Both of these functions may be encoded within one [[gene]], or alternatively the two functions may be encoded by separate genes. Two bacterial species that had diverged early in the course of evolution showing each of the alternative patterns were studied.<ref name = Huang1997>{{cite journal |vauthors=Huang Y, Braithwaite DK, Ito J |title=Evolution of dnaQ, the gene encoding the editing 3' to 5' exonuclease subunit of DNA polymerase III holoenzyme in Gram-negative bacteria |journal=FEBS Lett |volume=400 |issue=1 |pages=94–8 |date=January 1997 |pmid=9000520 |doi=10.1016/s0014-5793(96)01361-0 |url=}}</ref>  In the [[Gram-negative bacteria]] ''[[Salmonella]] typhimurium'' the 3’ to 5’ editing function employed during [[DNA replication]] is encoded by gene ''dnaQ'' which specifies a 3’ to 5’ exonuclease subunit, one of the three separately encoded core proteins of the DNA polymerase III holoenzyme.  The complete [[nucleic acid sequence|nucleotide sequence]] of ''dnaQ''  of ''S. typhimurium'' was determined.<ref name = Huang1997/>  The DNA polymerase from the early diverging bacterial species, ''[[Buchnera aphidicola]]'', was also sequenced. In this case, the DNA polymerase encoded by the DNA III (polC) gene contains both DNA polymerase and 3’ to 5’ exonuclease domains. This arrangement is in contrast to ''S. typhimurium'' in which these domains are encoded in separate genes.<ref name = Huang1997/>  Based on the sequence homologies found between the DNA regions encoding the 3’ to 5’ editing functions in these bacteria, it was proposed that a last common ancestor of ''S. typhimurium'' and ''B. aphidicola'' had a single gene containing both 3’ to 5’ exonuclease and DNA polymerase domains.  The evolutionary divergence of these bacteria (about 0.25 to 1.2 billion years ago), appears to have been associated with the separation of the DNA polymerase gene function from the 3’ to 5’ exonuclease editing gene function in the lineage containing ''S. typhimurium''.<ref name = Huang1997/>

== References ==
{{reflist|32em}}

== External links ==
* {{MeshName|dnaQ+protein,+E+coli}}

{{DNA replication}}

{{DEFAULTSORT:Dnaq}}
[[Category:DNA replication]]