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Molecular and Cellular Biology, October 2007, p. 7198-7205, Vol. 27, No. 20
0270-7306/07/$08.00+0     doi:10.1128/MCB.01079-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Role for Yeast and Human Translesion Synthesis DNA Polymerases in Promoting Replication through 3-Methyl Adenine

Robert E. Johnson, Sung-Lim Yu, Satya Prakash, and Louise Prakash^*

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-1061

Received 18 June 2007/ Returned for modification 5 July 2007/ Accepted 1 August 2007

3-Methyl adenine (3meA), a minor-groove DNA lesion, presents a strong block to synthesis by replicative DNA polymerases (Pols). To elucidate the means by which replication through this DNA lesion is mediated in eukaryotic cells, here we carry out genetic studies in the yeast Saccharomyces cerevisiae treated with the alkylating agent methyl methanesulfonate. From the studies presented here, we infer that replication through the 3meA lesion in yeast cells can be mediated by the action of three Rad6-Rad18-dependent pathways that include translesion synthesis (TLS) by Pol or - and an Mms2-Ubc13-Rad5-dependent pathway which presumably operates via template switching. We also express human Pols and in yeast cells and show that they too can mediate replication through the 3meA lesion in yeast cells, indicating a high degree of evolutionary conservation of the mechanisms that control TLS in yeast and human cells. We discuss these results in the context of previous observations that have been made for the roles of Pols , , and in promoting replication through the minor-groove N²-dG adducts.

Published ahead of print on 13 August 2007.

Present address: Department of Biological Sciences, Inha University, Incheon 402-751, Republic of Korea.

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