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J. Biol. Chem., Vol. 278, Issue 27, 24563-24576, July 4, 2003

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Enzymology of Base Excision Repair in the Hyperthermophilic Archaeon Pyrobaculum aerophilum^*

Alessandro A. Sartori and Josef Jiricny 

From the Institute of Molecular Cancer Research, University of Zürich, August Forel-Strasse 7, CH-8008 Zürich, Switzerland

DNA of all living organisms is constantly modified by exogenous and endogenous reagents. The mutagenic threat of modifications such as methylation, oxidation, and hydrolytic deamination of DNA bases is counteracted by base excision repair (BER). This process is initiated by the action of one of several DNA glycosylases, which removes the aberrant base and thus initiates a cascade of events that involves scission of the DNA backbone, removal of the baseless sugar-phosphate residue, filling in of the resulting single nucleotide gap, and ligation of the remaining nick. We were interested to find out how the BER process functions in hyperthermophiles, organisms growing at temperatures around 100 °C, where the rates of these spontaneous reactions are greatly accelerated. In our previous studies, we could show that the crenarchaeon Pyrobaculum aerophilum has at least three uracil-DNA glycosylases, Pa-UDGa, Pa-UDGb, and Pa-MIG, that can initiate the BER process by catalyzing the removal of uracil residues arising through the spontaneous deamination of cytosines. We now report that the genome of P. aerophilum encodes also the remaining functions necessary for BER and show that a system consisting of four P. aerophilum encoded enzymes, Pa-UDGb, AP endonuclease IV, DNA polymerase B2, and DNA ligase, can efficiently repair a G·U mispair in an oligonucleotide substrate to a G·C pair. Interestingly, the efficiency of the in vitro repair reaction was stimulated by Pa-PCNA1, the processivity clamp of DNA polymerases.

Received for publication, March 7, 2003 , and in revised form, April 18, 2003.

^* The work was supported by a grant from UBS AG (to A. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 41-1-634-8910; Fax: 41-1-634-8904; E-mail: jiricny{at}imr.unizh.ch.

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