Nucleic Acids Research Advance Access originally published online on November 21, 2007
Nucleic Acids Research 2008 36(3):705-711; doi:10.1093/nar/gkm1023
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Nucleic Acids Research, 2008, Vol. 36, No. 3 705-711
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nucleic Acid Enzymes |
Uracil recognition by replicative DNA polymerases is limited to the archaea, not occurring with bacteria and eukarya
1Institute for Cell and Molecular Biosciences (ICaMB), University of Newcastle, Newcastle upon Tyne NE2 4HH, UK, 2Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, MO 63110, 3Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA, 4Replizyme Ltd, York Science Park, York YO10 5DQ, UK, 5Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden and 6Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
*To whom correspondence should be addressed. Tel: +44 191 222 7371; Fax: +44 191 222 7424; Email: b.a.connolly{at}ncl.ac.uk
Received September 27, 2007. Revised October 26, 2007. Accepted October 27, 2007.
Family B DNA polymerases from archaea such as Pyrococcus furiosus, which live at temperatures 
100°C, specifically recognize uracil in DNA templates and stall replication in response to this base. Here it is demonstrated that interaction with uracil is not restricted to hyperthermophilic archaea and that the polymerase from mesophilic Methanosarcina acetivorans shows identical behaviour. The family B DNA polymerases replicate the genomes of archaea, one of the three fundamental domains of life. This publication further shows that the DNA replicating polymerases from the other two domains, bacteria (polymerase III) and eukaryotes (polymerases 
and 
for nuclear DNA and polymerase 
for mitochondrial) are also unable to recognize uracil. Uracil occurs in DNA as a result of deamination of cytosine, either in G:C base-pairs or, more rapidly, in single stranded regions produced, for example, during replication. The resulting G:U mis-pairs/single stranded uracils are promutagenic and, unless repaired, give rise to G:C to A:T transitions in 50% of the progeny. The confinement of uracil recognition to polymerases of the archaeal domain is discussed in terms of the DNA repair pathways necessary for the elimination of uracil.