], were recently described (6, 7). Thus, it is evident that protein inheritance is a widespread phenomenon, at least in lower eukaryotes.The discovery of prions in yeast occurred in different ways. Some (i.e., [PSI + ] and [URE3]) were long known as genetic determinants of mysterious nature until their prion nature was proposed (8). The others were revealed by purposeful screening of potentially prionogenic proteins and corresponding determinants. The prion-like determinant [ISP + ], described in our earlier work (9), belongs to the first group, because it was detected as a nonchromosomal antisuppressor in strains containing specific sup35 nonsense suppressor mutations and the nonsense mutations his7-1 (UAA) and lys2-87 (UGA (Fig. 1A). The Sup + phenotype cosegregated with Ura + in tetrads of the diploid that was obtained by crossing the sfp1Δ and [ISP + ] strains (Fig. 1B). These findings indicate either that [ISP + ] is a prion form of Sfp1 or that the change in phenotype was caused by an independent manifestation of the SFP1-null allele.To distinguish between these two possibilities, the sfp1Δ strain was transformed with the centromeric vector pRS315-SFP1. Introduction of the wild-type SFP1 allele did not change the phenotype of the sfp1Δ strain [i.e., the absolute majority (556 of 559) of transformants has retained the Sup + phenotype]. This fact suggests that the change of phenotype in the sfp1Δ strain was caused by [ISP + ] loss rather than phenotypic effects of the SFP1 deletion; otherwise, restoration of the Sup − phenotype would be observed. Notably, this loss was irreversible, because we have not observed a single example of Sup -clones appearing in the mitotic progeny of sfp1Δ strains in contrast to [isp -] strains obtained by GuHCl treatment, which produced Sup -clones at a high frequency (9). These results confirmed that SFP1 could be considered as a likely host gene for [ISP + ].

Clusters of localized hypermutation in human breast cancer genomes, named “kataegis” (from the Greek for thunderstorm), are hypothesized to result from multiple cytosine deaminations catalyzed by AID/APOBEC proteins. However, a direct link between APOBECs and kataegis is still lacking. We have sequenced the genomes of yeast mutants induced in diploids by expression of the gene for PmCDA1, a hypermutagenic deaminase from sea lamprey. Analysis of the distribution of 5,138 induced mutations revealed localized clusters very similar to those found in tumors. Our data provide evidence that unleashed cytosine deaminase activity is an evolutionary conserved, prominent source of genome-wide kataegis events.ReviewersThis article was reviewed by: Professor Sandor Pongor, Professor Shamil R. Sunyaev, and Dr Vladimir Kuznetsov.

We followed the deposition of protein, oil and fatty acids in developing seeds of ‘Acme,’ ‘Chippewa,’ and ‘Harosoy 63’ soybeans [Glycine max (L.) Merrill] to gain a better insight to the accumulation of these components. Nonprotein N and protein N were estimated by micro‐Kjeldahl procedure. Oil was determined by NMR, while fatty acids were analyzed by gas liquid chromatography.At approximately 25 days after flowering the composition of the seeds was about 30% protein and 5% oil; however, this represents only 2% of the total protein and 1% of the oil in the mature seed.From 24 to 40 days after flowering, oil percentage increased rapidly to 20%, which represents 30% of the total oil in the mature seed. The percentage of palmitic, stearic, and linolenic acid in the oil decreased, while the percentage of oleic and linoleic acid increased during this period. Although the percent values of the fatty acids changed markedly, actual amounts of all fatty acids increased. Percent nonprotein N decreased slightly, while percent protein N showed a concommittant rise from 24 to 40 days after flowering.During the remainder of the deevlopment (about 25 days) of the soybean seed, percent values of the components remained essentially constant. During this time, however, 70% of the total protein, oil, palmitic acid, oleic acid, and linoleic acid were synthesized, and 65% of the total stearic acid and 50% of the total linolenic acid also were synthesized.

Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. Initial nucleation of a yeast prion by transiently overproduced prion-forming protein or its (typically, QN-rich) prion domain is efficient only in the presence of another aggregated (in most cases, QN-rich) protein. Here, we demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non-QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation of Sup35 prions in the absence of preexisting aggregates. In contrast, both a fusion of the Sup35 prion domain to a multimeric nonamyloidogenic protein, and an expression of a mammalian amyloidogenic protein that is not fused to the Sup35 prion domain failed to promote prion nucleation, further indicating that physical linkage of a mammalian amyloidogenic protein to the prion domain of a yeast protein is required for the nucleation of a yeast prion. Biochemical and cytological approaches confirmed the nucleation of protein aggregates in the yeast cell. Sequence alterations antagonizing or enhancing amyloidogenicity of human β amyloid (Aβ, associated with Alzheimer disease) and mouse PrP (associated with prion diseases) respectively antagonized or enhanced nucleation of a yeast prion by these proteins. The yeast-based prion nucleation assay, developed in our work, can be employed for mutational dissection of amyloidogenic proteins. We anticipate that it will aid in the identification of chemicals that influence initial amyloid nucleation and in searching for new amyloidogenic proteins in a variety of proteomes.