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Bergoglio, V; Ferrari, E; Hübscher, U; Cazaux, C; Hoffmann, J S (2003). DNA polymerase beta can incorporate ribonucleotides during DNA synthesis of undamaged and CPD-damaged DNA. Journal of Molecular Biology, 331(5):1017-1023.

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Abstract

Overexpression of the error-prone DNA polymerase beta (Pol beta) has been found to increase spontaneous mutagenesis by competing with the replicative polymerases during DNA replication. Here, we investigate an additional mechanism potentially used by Pol beta to enhance genetic instability via its ability to incorporate ribonucleotides into DNA. By using an in vitro primer extension assay, we show that purified human and calf thymus Pol beta can synthesize up to 8-mer long RNA. Moreover, Pol beta can efficiently incorporate rCTP opposite G in the absence of dCTP and, to a lesser extent, rATP opposite T in the absence of dATP and rGTP opposite C in the absence of dGTP. Recently, Pol beta was shown to catalyze in vitro translesion replication of a thymine cyclobutane pyrimidine dimer (CPD). Here, we investigate if ribonucleotides could be incorporated opposite the CPD damage and modulate the efficiency of the bypass process. We find that all four rNTPs can be incorporated opposite the CPD lesion, and that this process affects translesion synthesis. We discuss how incorporation of ribonucleotides into DNA may contribute to the high frequency of mutagenesis observed in Pol beta up-regulating cells.

Item Type:Journal Article, refereed
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Biochemistry and Molecular Biology
DDC:570 Life sciences; biology
Language:English
Date:29 August 2003
Deposited On:11 Feb 2008 13:18
Last Modified:27 Nov 2013 23:01
Publisher:Elsevier
ISSN:0022-2836
Publisher DOI:10.1016/S0022-2836(03)00837-4
PubMed ID:12927538
Citations:Web of Science®. Times Cited: 14
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