of nucleotides in the cell are known to block DNA Department of Genetics, Harvard Medical School, 200 Longwood elongation (Vassilev and Russev, 1984; Friedberg et al Hartwell, 1995;Longhese et al., 1996). Here we rqh1 mutants. rqh1 ⍣ , previously known as hus2 ⍣ , demonstrate that reversible S phase arrest also requires encodes a putative DNA helicase related to the Escherprotective functions that are distinct from cell cycle ichia coli RecQ helicase, with particular homology to checkpoint controls. the gene products of the human BLM and WRN genesWe have previously studied S phase arrest in the fission and the Saccharomyces cerevisiae SGS1 gene. BLM and yeast Schizosaccharomyces pombe, by isolating mutants WRN are mutated in patients with Bloom's syndrome that are sensitive to hydroxyurea (HU), a drug that blocks and Werner's syndrome respectively. Both syndromes DNA replication by depleting deoxynucleotides. Our are associated with genomic instability and cancer screening strategy was based on the observation that susceptibility. We show that, like BLM and SGS1, checkpoint-defective cells undergo an aberrant mitosis rqh1 ⍣ is required to prevent recombination and that ('cut') when treated with HU (Enoch and Nurse, 1990). in fission yeast suppression of inappropriate recombinUnder the same conditions normal cells cease DNA ation is essential for reversible S phase arrest.synthesis and arrest cell division, displaying an elongated Keywords: cell cycle/hus2/recombination/RecQ DNA cell morphology. By screening for mutants that 'cut' in helicase/Schizosaccharomyces pombe HU, a number of checkpoint-defective HU-sensitive (hus) mutants were identified (Enoch et al., 1992). Several of the mutants were found to be allelic to previously known

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Genetic testing is becoming more widespread, and its capabilities and predictive power are growing. In this paper, we evaluate the ethical justifications for and strength of the US legal framework that aims to protect patients, research participants, and consumers from genetic discrimination in employment and health insurance settings in the context of advancing genetic technology. The Genetic Information Nondiscrimination Act (GINA) and other laws prohibit genetic and other health-related discrimination in the United States, but these laws have significant limitations, and some provisions are under threat. If accuracy and predictive power increase, specific instances of use of genetic information by employers may indeed become ethically justifiable; however, any changes to laws would need to be adopted cautiously, if at all, given that people have consented to genetic testing with the expectation that there would be no genetic discrimination in employment or health insurance settings. However, if our society values access to healthcare for both the healthy and the sick, we should uphold strict and broad prohibitions against genetic and health-related discrimination in the context of health insurance, including employer-based health insurance. This is an extremely important but often overlooked consideration in the current US debate on healthcare.

The fission yeast Rad3p checkpoint protein is a member of the phosphatidylinositol 3-kinaserelated family of protein kinases, which includes human ATMp. Mutation of the ATM gene is responsible for the disease ataxia-telangiectasia. The kinase domain of Rad3p has previously been shown to be essential for function. Here, we show that although this domain is necessary, it is not sufficient, because the isolated kinase domain does not have kinase activity in vitro and cannot complement a rad3 deletion strain. Using dominant negative alleles of rad3, we have identified two sites N-terminal to the conserved kinase domain that are essential for Rad3p function. One of these sites is the putative leucine zipper, which is conserved in other phosphatidylinositol 3-kinase-related family members. The other is a novel motif, which may also mediate Rad3p protein-protein interactions.