The structure of Jann_2411 (DUF1470) from Jannaschia sp. at 1.45 Å resolution reveals a new fold (the ABATE domain) and suggests its possible role as a transcription regulator

The crystal structure of the first representative of the Pfam PF07336 (DUF1470) family reveals a two-domain organization that contains a new fold, termed the ABATE domain, at the N-terminus and a treble-clef zinc finger that is likely to bind DNA at the C-terminus

A Systematic Analysis of Cell Cycle Regulators in Yeast Reveals That Most Factors Act Independently of Cell Size to Control Initiation of Division

Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms

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Network representation of the “Low G1” group.

<p>The interactions shown are from the gold-standard reference database BioGRID <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590-Stark1" target="_blank">[54]</a>. The network was constructed with Cytoscape <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590-Smoot1" target="_blank">[83]</a>, and displayed using an unbiased, force-generated layout. Only the factors that showed interactions (physical or functional) are included. We also included the essential gene <i>CDC28</i> (shown in red), encoding the major yeast Cdk.</p

Cys4p advances START both by promoting cell growth and by a separate function, which does not require CBS's catalytic activity.

<p>A, Rate of cell size increase (shown as growth rate, in fl/min) for the indicated strains was measured assuming linear growth from synchronous elutriated cultures in media that contain galactose and induce expression of the <i>P_GAL</i> alleles (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#s4" target="_blank">Methods</a>). The average value for each strain is shown with a horizontal bar (± sd). Where indicated, the <i>P</i> values shown were calculated from two-tailed <i>t</i> tests. The data used to calculate the values shown in A and B are in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590.s009" target="_blank">Figure S8</a>. B, The critical cell size of the indicated strains (shown in fl), was measured from the same elutriation experiments shown in A (see also <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590.s010" target="_blank">Figure S9</a>). The analogous experiments in non-inducing, glucose containing, medium are shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590.s010" target="_blank">Figure S9</a>.</p

Decreased fitness correlates with altered cell cycle progression.

<p>The y-axis shows the fitness values of Giaever et al <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590-Giaever1" target="_blank">[33]</a>. Higher values indicate reduced fitness. The cutoff for reduced fitness was about <85% of the wild type in that study <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590-Giaever1" target="_blank">[33]</a>. Thus, strains with possible small reductions in fitness have been assigned a “WT-like” fitness score of 1. Giaever et al <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590-Giaever1" target="_blank">[33]</a> evaluated fitness of the same strains we used, during growth in rich (YPD-2%Dextrose) liquid media, allowing for a direct comparison with our dataset. We used the non-parametric Spearman test to obtain the correlation (<i>r</i>) values we show. The correlation coefficient for all the strains (<i>r</i>_T) is shown at the bottom right of the graph. We colored the r values for the sub-groups as in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen-1002590-g002" target="_blank">Figure 2</a>. For every gene we included in this analysis, the values we used in this correlation are shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002590#pgen.1002590.s001" target="_blank">Dataset S1</a>.</p