A role for yeast and human translesion synthesis DNA polymerases in promoting replication through 3-methyl adenine.
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(eta) or -zeta and an Mms2-Ubc13-Rad5-dependent pathway which presumably operates via template switching. We also express human Pols iota and kappa 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 eta, iota, and kappa in promoting replication through the minor-groove N2-dG adducts.
Johnson
Robert E
RE
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555-1061, USA.
Yu
Sung-Lim
SL
Prakash
Satya
S
Prakash
Louise
L
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000378:metabolism; D001665:Binding Sites; D004265:DNA Helicases; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D018906:Antineoplastic Agents, Alkylating; D007527:Isoenzymes; C112520:MMS2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C025946:3-methyladenine; D008741:Methyl Methanesulfonate; C471610:UBC13 protein, S cerevisiae; C471607:UBE2N protein, human; C114715:UBE2V2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D004259:DNA-Directed DNA Polymerase; D000251:Adenosine Triphosphatases; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases; D008025:Ligases; D000225:Adenine
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