Article: Sensitivity to Phosphonoacetic Acid: A New Phenotype to Probe DNA Polymerase [delta] in Saccharomyces cerevisiae

ABSTRACT

A mutant allele (pol3-L612M) of the DNA polymerase δ gene in Saccharomyces cerevisiae that confers sensitivity to the antiviral drug phosphonoacetic acid (PAA) was constructed. We report that PAA-sensitivity tagging DNA polymerases is a useful method for selectively and reversibly inhibiting one type of DNA polymerase. Our initial studies reveal that replication by the L612M-DNA pol δ requires Rad27 flap endonuclease activity since the pol3-L612M strain is not viable in the absence of RAD27 function. The L612M-DNA pol δ also strongly depends on mismatch repair (MMR). Reduced viability is observed in the absence of any of the core MMR proteins-Msh2, Mlh1, or Pms1-and ...

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