Tension stabilizes the attachment of microtubules to kinetochores during cell division in budding yeast, demonstrating how mechanical forces can modulate chromosome movement during replication. Researchers identify a new inhibitor of an enzyme that helps control mitosis by suppressing the activity of cyclin-dependent kinase 1, a key regulator of mitotic entry, revealing a completely novel component of the mitotic control system.
A truncated and oncogenic form of the epidermal growth factor receptor EGFRvIII associated with aggressive human brain tumors (gliomas) can be transferred from cell to cell by membrane-derived microvesicles known as oncosomes, possibly explaining why only a small percentage of glioma cells actually express EGFRvIII. Microtubule-targeted anti-tumor drugs, which are prescribed to treat a variety of cancers, work by arresting mitosis and inducing cell death, but the exact mechanism of this action is not well understood, nor are the molecular details of how some tumor cells seem resistant to the drugs. These papers identify a critical regulator of apoptosis induced by such drugs, a pro-survival protein called MCL1, which is degraded by ubiquitin ligase FBW7 to mediate cell death. Some leukemia cell lines deficient in FBW7 have high expression levels of MCL1 and are able to evade apoptosis when treated with a treatment that targets MCL1. The results have implications for improving certain anti-tumor therapies, and suggest that both MCL1 and FBW7 could serve as potential biomarkers of a patient's response to microtubule-targeted agents.
Researchers uncover the mechanism of DNA topoisomerase II's ability to unravel the DNA of sister chromatids in yeast cells before segregation during cell division: Mitotic spindles and the condensin factor Smc2 trigger the positive supercoiling of each sister chromatid, at which point topoisomerase II separates the molecules.
DNA double-strand breaks are sometimes left unrepaired, which can result in the addition of telomeres in the middle of chromosomes and gross chromosomal rearrangements. Here, the researchers identify a novel mechanism by which yeast cells prevent such inappropriate telomere addition, involving the Mec1 kinase, the yeast protein phosphatase 4 (PP4), and telomerase recruitment protein Cdc13, which helps to maintain genome integrity.
The F1000 Top 7 is a snapshot of the highest ranked articles from a 30-day period on Faculty of 1000 Cancer Biology and, as calculated on March 24, 2011. Faculty Members evaluate and rate the most important papers in their field.