MCB Accepts, published online ahead of print on 20 August 2007

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Mol. Cell. Biol. doi:10.1128/MCB.01079-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. 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, USA

^* To whom correspondence should be addressed. Email: l.prakash{at}utmb.edu.

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 (MMS). 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 Pols 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.

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