The entire DNA sequence of chromosome III of the yeast Saccharomyces cerevisiae has been determined. This is the first complete sequence analysis of an entire chromosome from any organism. The 315-kilobase sequence reveals 182 open reading frames for proteins longer than 100 amino acids, of which 37 correspond to known genes and 29 more show some similarity to sequences in databases. Of 55 new open reading frames analysed by gene disruption, three are essential genes; of 42 non-essential genes that were tested, 14 show some discernible effect on phenotype and the remaining 28 have no overt function.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria.

The Cephalotaxus alkaloids harringtonine, homoharringtonine and isoharringtonine inhibit protein synthesis in eukaryotic cells. The alkaloids do not inhibit, in model systems, any of the steps of the initiation process but block poly(U)-directed polyphenylalanine synthesis as well as peptide bond formation in the fragment reaction assay, the sparsomycin-induced binding of (C)U-A-C-C-ArH]Leu-Ac, and the enzymic and the non-enzymic binding of Phe-tRNA to ribosomes. These results suggest that the Cephalotaxus alkaloids inhibit the elongation phase of translation by preventing substrate binding to the acceptor site on the 60-S ribosome subunit and therefore block aminoacyltRNA binding and peptide bond formation.However, the Cephalotaxus alkaloids do not inhibit polypeptide synthesis and peptidyl-[3H]puromycin formation in polysomes. Furthermore, these alkaloids strongly inhibit [14C]trichodermin binding to free ribosomes but hardly affect the interaction of the antibiotic with yeast polysomes. These results clearly suggest that the Cephalotaxus alkaloids cannot interact with polysomes and therefore only inhibit the initial cycles of elongation. This explains the polysome run off that has been observed by some workers in the presence of harringtonine.Harringtonine, homoharringtonine and isoharringtonine are alkaloids from Cephalotaxus harringtonia [l]. These three compounds have an antitumour activity and differ only in a side chain whereas the alkaloid lacking the side chain is inactive [2]. The antitumour activity of these alkaloids is due to their inhibitory effect on protein synthesis [2]. It has been proposed that these alkaloids inhibit the initiation of polypeptide synthesis since they induce the breakdown of polysomes to ribosomes in intact cells and cell lysatesWe have sequentially studied the individual steps of translation to elucidate the specific step(s) inhibited by the Cephalotaxus alkaloids. The results presented here show that these compounds do not inhibit initiation but block peptide bond formation and aminoacyltRNA binding.