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Uracil recognition by replicative DNA polymerases is limited to the archaea, not occurring with bacteria and eukarya

Lookup NU author(s): Dr Josephine Wardle, Pauline Heslop, Professor Bernard Connolly

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Abstract

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 δ and ε for nuclear DNA and polymerase γ 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. © 2007 The Author(s).


Publication metadata

Author(s): Wardle J, Burgers P, Cann I, Darley K, Heslop P, Johansson E, Lin L, McGlynn P, Sanvoisin J, Stith C, Connolly B

Publication type: Article

Publication status: Published

Journal: Nucleic Acids Research

Year: 2008

Volume: 36

Issue: 3

Pages: 705-711

Print publication date: 01/02/2008

ISSN (print): 0305-1048

ISSN (electronic): 1362-4962

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/nar/gkm1023

DOI: 10.1093/nar/gkm1023

PubMed id: 18032433


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Funding

Funder referenceFunder name
G0000076Medical Research Council
GM 32431NIGMS NIH HHS
R01 GM032431NIGMS NIH HHS

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