1. Powerful tension
 |
Image of mitotic spindle in a human cell: microtubules in green, chromosomes in blue, and kinetochores in red.
Image: Wikimedia commons, Afunguy | Tension stabilizes the attachment of microtubules to kinetochores during cell division in budding yeast, demonstrating how mechanical forces can modulate chromosome movement during replication. B. Akiyoshi, et al., "Tension directly stabilizes reconstituted kinetochore-microtubule attachments," Nature, 468:576-9. 2010. Evaluations by Claire Walczak, Indiana Univ; William Earnshaw, Univ Edinburgh; Raquel Oliveira, Univ Oxford; Yamini Dalal, NCI; Eugenio Marco and Gaudenz Danuser, Harvard Med Sch; Jonathan Millar, Univ Warwick; Iain Cheeseman, MIT. Free F1000 Evaluation 2. Mitosis mechanism discovered 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. S. Mochida et al., "Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis," Science, 330:1670-3, 2010. Evaluations by Matthew Mazalouskas and Brian Wadzinski, Vanderbilt Univ; Mar?al Vilar and Angel Nebreda, Inst for Research in Biomed; Marie-Emilie Terret and Marie-H?l?ne Verlhac, CIRB, College de France. Free F1000 evaluation 3. Cancer contagious among cells 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. K. Al-Nedawi et al., "Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells," Nat Cell Biol,, 10:619-24, 2008. Evaluations by Clotilde Thery, Curie Inst; Michael Gold, Univ British Columbia; Ross Cagan, Mount Sinai Sch of Med; Harald Stenmark, The Norwegian Radium Hosp. Free F1000 evaluation 4 and 5. Mechanism of anti-tumoral drugs unveiled 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. I.E. Wertz et al., "Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7," Nature, 471:110-4, 2011. Evaluated by Laura Diaz Martinez and Duncan Clarke, Univ Minnesota; Loretta Dorstyn and Sharad Kumar, Cen for Cancer Bio. Free F1000 evaluation
H. Inuzuka et al., "SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction," Nature, 471:104-9, 2011. Evaluated by Laura Diaz Martinez and Duncan Clarke, Univ Minnesota; Loretta Dorstyn and Sharad Kumar, Cen for Cancer Bio. Free F1000 evaluation 6. Supercoiling sister chromatids 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. J. Baxter et al., "Positive supercoiling of mitotic DNA drives decatenation by topoisomerase II in eukaryotes," Science, 331:1328-32, 2011. Evaluations by Olivier Hyrien, Institut de Biologie de l'ENS, CNRS. Free F1000 evaluation 7. Preventing ill-placed telomeres 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. W. Zhang and D. Durocher, "De novo telomere formation is suppressed by the Mec1-dependent inhibition of Cdc13 accumulation at DNA breaks," Genes Dev, 24:502-15, 2010. Evaluations by David Shore, Univ Geneva; Katherine Friedman, Vanderbilt Univ; Yun Wu and Virginia Zakian, Princeton Univ. Free F1000 evaluation 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. To see the latest rankings, search the database, and read daily evaluations, visit http://f1000.com. Related stories:
Top 7 in medicine
[22nd March 2011]
Top 7 in biochemistry
[15th March 2011]
Top 7 in immunology
[8th March 2011] |
