New & Noteworthy
March 5, 2013
Sixty new datasets have been added to our expression analysis tool at SGD, facilitating the rapid identification of co-expressed genes based on patterns of expression shared with query gene(s) across the entire collection. Expression data are now available at SGD from a comprehensive collection of 430 datasets representing 9190 microarrays from a total of 286 publications. The expression analysis tool can be accessed via the Expression tab and Expression Summary histogram located on Locus Summary pages, or using the ‘Expression’ option in the Function pulldown in the menu bar at the top of SGD pages. The new data will by default be included with the previous data when using the ‘New Search’, ‘Show Expression Levels’, or ‘Dataset Listing’ options. Alternatively, the new datasets can be specifically filtered using the dataset tag ‘not yet curated’. All of the RNA expression data are available for download in expression directory. Datasets are grouped by publication and are in PCL format.
March 5, 2013
Cancer often gets going with chromosome instability. Basically a cell gets a mutation that causes its chromosomes to mutate at a higher rate. Now it and any cells that come from it build mutations faster and faster until they hit on the right combination to make the cell cancerous. An accelerating avalanche of mutations has led to cancer.
There are plenty of obvious candidates for the genes that start these avalanches: genes like those involved in segregating chromosomes and repairing DNA, for example. But there are undoubtedly sleeper genes that no one has really thought of. In a new study out in GENETICS, Minaker and coworkers have used the yeast S. cerevisiae to identify three of these genes — GPN1 (previously named NPA3), GPN2, and GPN3.
A mutation in any one of these genes leads to chromosomal problems. For example, mutations in GPN1 and GPN2 cause defects in sister chromatid cohesion and mutations in GPN3 confer a visible chromosome transmission defect. All of the mutants also show increased sensitivity to hydroxyurea and ultraviolet light, two potent mutagens. And if two of the genes are mutated at once, these defects become more severe. Clearly, mutating GPN1, GPN2, and/or GPN3 leads to an increased risk for even more mutations!
What makes this surprising is what these genes actually do in a cell. They are responsible for getting RNA polymerase II (RNAPII) and RNA polymerase III (RNAPIII) into the nucleus and assembled properly. This was known before for GPN1, but here the authors show that in gpn2 and gpn3 mutants, RNAPII and RNAPIII subunits also fail to get into the nucleus. Genetic and physical interactions between all three GPN proteins suggest that they work together in overlapping ways to get enough RNAPII and RNAPIII chugging away in the nucleus.
So it looks like having too little RNAPII and RNAPIII in the nucleus causes chromosome instability. This is consistent with previous work that shows that mutations in many of the RNAPII subunits have similar effects. Still, these genes would not be the first ones most scientists would look at when trying to find causes of chromosomal instability. Score another point for unbiased screens in yeast leading to a better understanding of human disease.