3 Cellular Responses to DNA Damage in Yeast

Abstract

I. INTRODUCTION
The general topic of cellular responses to DNA damage in the yeast Saccharomyces cerevisiae has been reviewed in several contexts (Lemontt 1980; Haynes and Kunz 1981; Lawrence 1982; Friedberg 1985a,b, 1988; von Borstel and Hastings 1985; Cooper and Kelly 1987; Moustacchi 1987). These reviews have documented the basic genetics and general biology of DNA repair and mutagenesis. In 1991, the essential question is no longer what are the phenomena of DNA repair and mutagenesis in yeast, but, rather, how are these elements of DNA metabolism transacted at the molecular level? Although the answers to this question are far from complete, the emphasis of this chapter is on the molecular biology and biochemistry of cellular responses to DNA damage, in keeping with the intended focus of these volumes.

Strictly defined, the term DNA repair refers to cellular events associated with the removal of damaged, inappropriate, or mispaired bases from the genome of living cells (see Friedberg 1985a). In this narrow context, the topic is confined to (1) DNA damage reversal (e.g., monomerization of cyclobutyldipyrimidines [pyrimidine dimers] by DNA photolyase or demethylation of methylated [alkylated] bases by specific DNA methyltransferases); (2) base excision repair, whereby damaged bases (e.g., alkylated) or inappropriate bases (e.g., uracil) are excised by specific classes of repair enzymes designated DNA glycosylases and AP (apurinic/apyrimidinic) endonucleases; (3) nucleotide excision repair, whereby oligonucleotide tracts containing distortive bulky base adducts are excised; and (4) mismatch repair, whereby mismatched bases generated during semiconservative DNA synthesis or during recombination are excised.