17 Responses to Aberrant DNA Replication and DNA Damage in Yeasts

Abstract

This chapter and chapter 18 deal with eukaryotic cellular responses to abnormal replication and DNA damage during S phase. This chapter is focused on responses in yeasts, whereas Chapter 18 describes responses in animals. In both yeasts and animals, responses to stalled replication forks and DNA damage are mediated in part by checkpoint mechanisms that retard replication and inhibit mitosis and in part by checkpoint-independent mechanisms. Whether checkpoint-dependent or -independent, the basic features of these responses are frequently conserved among eukaryotic organisms; however, as the reader of these two chapters will find, there are in some cases significant differences in details. Thus, a much more complete understanding of eukaryotic responses to abnormal replication and DNA damage during S phase can be obtained by reading both chapters than by focusing on results obtained in any single organism.

OVERVIEW OF DNA-INTEGRITY CHECKPOINTS IN BUDDING AND FISSION YEASTS
Checkpoint pathways in budding yeast (Saccharomyces cerevisiae) and in fission yeast (Schizosaccharomyces pombe) are responsible for generation of responses to (1) normal replication forks, (2) forks stalled by treatment of cells with the ribonucleotide reductase inhibitor, hydroxyurea (HU), (3) forks stalled by damage in the template DNA, and (4) damaged sites that are not associated with replication forks, in S and G₂ phases (Fig. 1). The diagrams in Figure 1 are based on previous research, which is summarized in recent reviews (Boddy and Russell 1999; Huberman 1999; Caspari et al. 2000; Foiani et al. 2000; O’Connell et al. 2000; Rhind et al. 2000; Carr 2002;...