Three cellular processes—cell shape, interphase microtubule organization, and cell-cycle progression—appear to share unexpected links. According to researchers at the University of Cambridge, these processes rely on many of the same genes.
To arrive at this finding, the researchers, led by Rafael Carazo Salas, Ph.D., from the Department of Genetics, combined high-resolution 3D confocal microscopy and computer-automated analysis of the images to survey the fission yeast genome. This approach allowed the researchers to manipulate a single gene at a time and see simultaneously how this affected the three cellular processes.
The researchers published their results October 27 in Developmental Cell, in an article entitled, “A Genomic Multiprocess Survey of Machineries that Control and Link Cell Shape, Microtubule Organization, and Cell-Cycle Progression.”
“We identify, validate, and functionally annotate 262 genes controlling specific aspects of those processes,” wrote the authors. “Of these, 62% had not been linked to these processes before and 35% are implicated in multiple processes.”
The researchers emphasized that their technique not only allowed them to identify the functions of hundreds of genes across the genome, it also made it possible for them to systematically ask how the processes might be linked. For example, they found in the yeast—and, importantly, validated in human cells—a previously unknown link between control of microtubule stability and the machinery that repairs damage to DNA.
Many conventional cancer therapies target microtubular stability or DNA damage. Although evidence in the scientific literature suggests that drugs targeting both processes interact, the reason why has been unclear.
In addition, the researchers found that disruption of cell-cycle progression did not necessarily affect cell size control and that “distinct aspects of cell shape regulate microtubules and vice versa, identifying important systems-level links across these processes.”
“Both the technique and the data it produces are likely to be a very valuable resource to the scientific community in the future,” said Dr. Carazo Salas. “It allows us to shine a light into the black box of the genome and learn exciting new information about the basic building blocks of life and the complex ways in which they interact.”
All the data from the study is being published online as an open resource for researchers to use. It will be available online at www.sysgro.org.