537 research outputs found
Short- and long-term effects of chromosome mis-segregation and aneuploidy
No full textDividing cells that experience chromosome mis-segregation generate aneuploid daughter cells, which contain an incorrect number of chromosomes. Although aneuploidy interferes with the proliferation of untransformed cells, it is also, paradoxically, a hallmark of cancer, a disease defined by increased proliferative potential. These contradictory effects are also observed in mouse models of chromosome instability (CIN). CIN can inhibit and promote tumorigenesis. Recent work has provided insights into the cellular consequences of CIN and aneuploidy. Chromosome mis-segregation per se can alter the genome in many more ways than just causing the gain or loss of chromosomes. The short- and long-term effects of aneuploidy are caused by gene-specific effects and a stereotypic aneuploidy stress response. Importantly, these recent findings provide insights into the role of aneuploidy in tumorigenesis.National Institutes of Health (U.S.) (Grant GM56800
Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit
No full textIn budding yeast, a Ras-like GTPase signaling cascade known as the mitotic exit network (MEN) promotes exit from mitosis. To ensure the accurate execution of mitosis, MEN activity is coordinated with other cellular events and restricted to anaphase. The MEN GTPase Tem1 has been assumed to be the central switch in MEN regulation. We show here that during an unperturbed cell cycle, restricting MEN activity to anaphase can occur in a Tem1 GTPase-independent manner. We found that the anaphase-specific activation of the MEN in the absence of Tem1 is controlled by the Polo kinase Cdc5. We further show that both Tem1 and Cdc5 are required to recruit the MEN kinase Cdc15 to spindle pole bodies, which is both necessary and sufficient to induce MEN signaling. Thus, Cdc15 functions as a coincidence detector of two essential cell cycle oscillators: the Polo kinase Cdc5 synthesis/degradation cycle and the Tem1 G-protein cycle. The Cdc15-dependent integration of these temporal (Cdc5 and Tem1 activity) and spatial (Tem1 activity) signals ensures that exit from mitosis occurs only after proper genome partitioning.National Institutes of Health (U.S.) (GM056800)National Science Foundation (U.S.). Predoctoral Fellowshi
Aneuploidy triggers a TFEB-mediated lysosomal stress response
No full textAneuploidy, defined as an alteration in chromosome number that is not a multiple of the haploid complement, severely affects cellular physiology. Changes in chromosome number lead to imbalances in cellular protein composition, thus disrupting cellular processes and causing proteins to misfold and aggregate. We recently reported that in mammalian cells protein aggregates are readily encapsulated within autophagosomes but are not degraded by lysosomes. This leads to a lysosomal stress response in which the transcription factor TFEB induces expression of factors needed for macroautophagy-mediated protein degradation. Our studies uncover lysosomal degradation defects as a feature of the aneuploid state, and a role for the transcription factor TFEB in the response thereto.
Keywords: aneuploidy; autophagy; cancer; proteotoxicity; TFE
Angelika Amon: Conquering the divide
No full textAmon studies how cells segregate their chromosomes and what happens when they get it wrong.</jats:p
New Insights into the Troubles of Aneuploidy
No full textDeviation from a balanced genome by either gain or loss of entire chromosomes is generally tolerated poorly in all eukaryotic systems studied to date. Errors in mitotic or meiotic cell division lead to aneuploidy, which places a burden of additional or insufficient gene products from the missegregated chromosomes on the daughter cells. The burden of aneuploidy often manifests itself as impaired fitness of individual cells and whole organisms, in which abnormal development is also characteristic. However, most human cancers, noted for their rapid growth, also display various levels of aneuploidy. Here we discuss the detrimental, potentially beneficial, and sometimes puzzling effects of aneuploidy on cellular and organismal fitness and tissue function as well as its role in diseases such as cancer and neurodegeneration.National Institutes of Health (U.S.) (Grant GM56800
Life and death decisions
No full textCells must perpetually decide on three big choices in life: to grow, to divide or to die. These
system-level decisions are the output of a complex and still very poorly understood molecular
algorithm, which is built from many different sub-routines. Biochemical and genetic insights,
sometimes coupled with good fortune, have illuminated key individual steps in the networks that
dictate growth, division and death. Increasingly, the complex relationships between these
discrete steps have begun to emerge from the convolved mists of evolutionary construction. A
building ueber-theme is the unexpectedly deep integration of division, growth and death not only with each other, but with cellular metabolism. As covered in this Current Opinion in Cell Biology, this full-on system-wide view of the cell is poised to address both the how and why of big decisions in the life of a cell
Oral History Interview, Angelika Bammer (1470)
No full textIn this interview, Angelika Bammer discusses her time obtaining her PhD in Comparative Literature at UW-Madison. She also details her career becoming an author and the process that entails. To learn more about this oral history, download & review the index first (or transcript if available). It will help determine which audio file(s) to download & listen to.Angelika Bammer was born in Germany. She studied at the University of Heidelberg before she earned her PhD in Comparative Literature at the University of Wisconsin-Madison. Bammer is the author of Partial Visions: Feminism and Utopianism in the 1970’s (1991). She is currently an Associate Professor of Interdisciplinary Humanities at Emory College of Arts and Sciences, and a member in the Department of Comparative Literature
A case for more curiosity-driven basic research
No full textHaving been selected to be among the exquisitely talented scientists who won the Sandra K. Masur Senior Leadership Award is a tremendous honor. I would like to take this opportunity to make the case for a conviction of mine that I think many will consider outdated. I am convinced that we need more curiosity-driven basic research aimed at understanding the principles governing life. The reasons are simple: 1) we need to learn more about the world around us; and 2) a robust and diverse basic research enterprise will bring ideas and approaches essential for developing new medicines and improving the lives of humankind
Angelika Amon (1967–2020): Breakthrough scientist, extraordinary mentor, and loyal friend
No full textWhen asked to write a tribute to our mentor and friend, Angelika, 20 years of memorable, funny, and exciting anecdotes came to mind, some of which we recount below.Angelika Amon was born in Vienna, Austria on January 10, 1967, and was attracted to science for as long as she could remember. Passionate, exuberant, and incorrigibly curious, it is easy to imagine young Angelika bursting with “why” questions. Brought up in a family fostering her love for animals and nature, she aspired to be a zoologist at first, but ended up devoting her life to discovering the fundamental concepts of biology. In high school, a black and white movie from the fifties showing chromosomes splitting apart enchanted Angelika and drew her to molecular biology and genetics. “The way nature works is unmatched and cells work perfectly,” she used to say with contagious enthusiasm. Determined to pursue her dream, for her undergraduate thesis she marched—no doubt about that—into Kim Nasmyth’s office at the Institute of Molecular Pathology in Vienna. At that time, Kim was new to the city and country, and, by Angelika's account, it was her knowledge of the Austrian waltz and German language that won her a place in his laboratory. She remained there for her PhD, graduating in 1993. From the early days in Kim’s laboratory, Angelika distinguished herself as one of the brightest minds of the cell cycle field. Using the elegant genetics of budding yeast, Angelika made key contributions to our understanding of cell cycle control. She showed that cyclins are confined within precise cell cycle windows by a combination of transcriptional and posttranslational regulatory mechanisms. On the one hand, cyclins self-regulate at the transcriptional level via sophisticated feedback loops; on the other, they undergo ubiquitin-mediated degradation to allow exit from mitosis. She went on to show how this degradation is turned off to allow entry into the next cell cycle (1)
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