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  • Chromosomes are responsible for a critical enzyme’s activation during cell division | Newswire
    chromosomes and lead to cancer or other diseases So researchers are concentrating on every step of the process trying to learn as much as they can about how cells divide and which molecules are involved Assistant Professor Hironori Funabiki head of the Laboratory of Chromosome and Cell Biology is particularly interested in how chromosomes are responsible for directing cell division and in how microtubules form the bipolar spindle The latter is the critical step that allows the chromosomes to align and involves at least three cellular pathways one of which the chromosomal passenger complex or CPC Funabiki recently discovered The CPC is a group of proteins that bind to chromosomes as they re lined up along the cell s center in preparation for division The new research from Funabiki Alex Kelly a postdoctoral fellow in his lab and their colleagues shows that the ability of the bipolar spindle to assemble only in the presence of chromosomal DNA can be pinned on a specific enzyme in the CPC the Aurora B kinase Kelly and Funabiki found that spindle formation requires multiple molecules of Aurora B and that the presence of chromosomes greatly increases the probability that numerous molecules will be found in one place In order for the kinase to be fully activated a protein called Incenp must bind to and receive a phosphate group But once the two molecules are bound their conformation leaves them too far away from each other to completely transfer the phosphate group and they have to bring another Aurora B molecule in for total activation In research reported in Developmental Cell Funabiki and Kelly show that because a cell s chromosomal DNA has many sites at which the CPC can attach the presence of chromosomes therefore increases the frequency with which Aurora B molecules can

    Original URL path: http://newswire.rockefeller.edu/2007/07/30/chromosomes-are-responsible-for-a-critical-enzymes-activation-during-cell-division/ (2016-02-13)
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  • Rockefeller researchers show evidence of asymmetric cell division in mammalian skin | Newswire
    harmful bacteria out says Fuchs who is the Rebecca C Lancefield Professor and head of the Laboratory of Mammalian Cell Biology at Rockefeller Through experiments in cell culture in the 1980s everyone believed that the epidermis maintained its protective function by ejecting cells from the basal layer and forcing them upward Our data show that asymmetric divisions occur perpendicular to the basal layer resulting in one of the two daughter cells being naturally displaced out of the basal layer This opens up new ways to approach the pathology of different skin diseases and provides an explanation for how stem cells might generate one new stem cell and one differentiating cell at the same time Lechler first documented how often he saw cells in the basal layer of skin in mice dividing perpendicularly to the basement membrane below the bottom layer of cells He found that at least 75 percent of all the cell divisions he observed were in this orientation It was obvious from the first few mice that I looked at that not only did perpendicular divisions occur but they were extremely common says Lechler We can t rule out that some cells detach from the bottom layer and migrate upwards but this is most likely a minor component of skin stratification He then turned to flies for help Asymmetric divisions and the proteins involved in selecting the division direction are well documented in fruit flies Specifically the proteins Inscuteable and Pins form a complex that anchors one pole of the machinery that drives division to the top or apical side of the cell leaving the other pole at the base of the cell This defines the axis of the division plane Lechler found the mammalian equivalents of these proteins and looked to see whether or not they were involved Anywhere Terry saw a cell whose division plane was oriented perpendicular to the basal layer he saw the Inscuteable complex forming on the apical side of the cell Fuchs says It was the first time that this complex involved in asymmetric divisions in fruit flies has been implicated in a similar fashion in mice And it is fascinating that asymmetric divisions turn out to control skin differentiation But not everything works exactly the same Lechler also discovered that integrin and cadherin proteins contribute to the asymmetric divisions in the epidermis Integrins are proteins that anchor cells in the bottom epidermal layer to the basement membrane and cadherins are important in maintaining adhesion between cells so they can create the barrier that keeps harmful bacteria out Neither have been previously shown to be involved in asymmetric divisions in the fly However in mice if these proteins are mutated or missing the cells don t divide properly Our data help us to understand how cells are able to detach from the basement layer and move upward Fuchs says When the cells divide asymmetrically so that one daughter cell sits atop of the other the cell on top is already detached from

    Original URL path: http://newswire.rockefeller.edu/2005/08/15/rockefeller-researchers-show-evidence-of-asymmetric-cell-division-in-mammalian-skin/ (2016-02-13)
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  • Preparing for a safe split | Newswire
    from egg cells of the African clawed frog Xenopus laevis that were kept in metaphase the stage of cell division at which spindle chromosome connections are formed They identified two new related proteins which they named Dasra A and Dasra B Funabiki says he wants to know if these newly discovered proteins may represent a control mechanism in cancer development The Dasra proteins also exist in many other species From database searches Funabiki and his coworkers identified Dasra A in amphibians fish and chicken species in which early embryonic cells divide frequently By contrast they found that humans and other mammals in which embryonic development is slow appear to produce only Dasra B We speculate that there are different needs in different organisms and that Dasra A is specifically functioning during rapid embryonic divisions says Sampath Species that reproduce in large numbers such as animals that lay many eggs in the open favor rapid development over well controlled but slower cell division He suggests that Dasra A may be related to the apparently less stringent quality control of cell division in these species Funabiki and his coworkers discovered that Dasra A and Dasra B are components of the chromosomal passenger complex an assembly of proteins that bind to chromosomes during metaphase to help organize chromosomes within the cell as it divides This discovery led the scientists to study the role of the chromosomal passenger complex in spindle formation The spindle consists of microtubule polymers that span the cell and attach to structures called centrosomes located at opposing ends of a dividing cell Microtubules normally act like railway tracks in cells enabling transport of cellular material During cell division however the microtubule networks disassemble or depolymerize and reassemble to form the spindle framework During metaphase a chromosome pair usually appears as a characteristic X shaped structure held together at the waist or centromere Funabiki and his team studied a laboratory system which contained neither centromeres nor the centrosomes that anchor the spindle framework They demonstrated that the chromosomal passenger complex is necessary for spindle assembly in these chromosomes They also showed that the passenger complex regulates the activity of a protein that depolymerizes microtubules called MCAK mitotic centromere associated kinesin In their Cell paper Funabiki and his colleagues propose that the chromosomal passenger complex inhibits the microtubule degrading activity of MCAK around spindle attachment points Inactivation of MCAK thus permits microtubules to polymerize and to form stable connections with the chromosomes The chromosomal passenger complex contains a protein called Aurora B This protein is thought to play a role in the control of microtubule stability around centromeres Funabiki and his coworkers present new evidence that Aurora B is also a key player in regulating spindle growth around the arms of chromosomes It is possible Sampath says that the cell cycle control activity of Aurora B is in turn regulated by the Dasra proteins Organisms that reproduce sexually use two schemes for cell division Somatic cells divide through mitosis whereas germ cells

    Original URL path: http://newswire.rockefeller.edu/2004/07/23/preparing-for-a-safe-split/ (2016-02-13)
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  • What inspires yeast cells to divide? | Newswire
    how the cell cycle may normally work in humans as well as how it might malfunction in cancer How cells reproduce Professor Fred Cross and Ralph Wäsch were surprised to find that old models of cellular division in yeast do not hold true All eukaryotic cells cells that contain a nucleus must undergo some form of a cell cycle in order to grow and reproduce During this process two crucial events must occur within a cell s nucleus replication of the DNA called S phase and separation of the resulting chromosomes into two groups called mitosis or M phase Completing the cell cycle are two periods of rest which take place just before both S and M phase and are called G1 and G2 respectively Only when the cell senses that these events have transpired without error will it exit mitosis and divide into two daughter cells At this point the process either begins anew or a cell enters a state of dormancy called G0 How a cell moves from one phase to the next depends on periodic waves of cyclins low levels prepare DNA for replication higher levels trigger S phase and mitosis and a drastic drop in cyclin number signals the cell to begin dividing Equally important to this process are the proteins that cyclins bind to and activate called cyclin dependent kinases CDKs Once activated CDKs carry out the specific cellular tasks required for growth and division Cancer arises when the body fails to properly regulate this process For example healthy cells respond to DNA damaging agents such as sunlight or cigarette smoke by halting their cell cycle while the damage is repaired or by committing a type of cell suicide called apoptosis But cancerous cells have lost this system of checks and balances resulting in uncontrolled cell growth DNA damage and eventually tumors This breakdown in the cell cycle is caused by genetic mutations that lead to abnormal quantities of cell cycle proteins such as the cyclins Cellular oscillators The latest findings also suggest a new way of thinking about a yeast cell s oscillators Oscillators are protein complexes that control the ebb and flow of cyclins within a cell s nucleus thereby ensuring an orderly progression through the cell cycle During mitosis they signal the cell to destroy certain cyclins which then forces it to exit mitosis and begin division In both human and yeast cells there are two oscillators the Cdc20 oscillator and the Cdh1 oscillator Previously scientists thought that the Cdc20 oscillator controlled chromosome separation as well as mitotic exit via elimination of Clb5 while the Cdh1 oscillator was thought to complete exit from mitosis by destroying Clb2 But the new Nature report tells a different story It shows that the Cdc20 oscillator dictates exit from mitosis via elimination of Clb2 not Clb5 Previous experiments showing the destruction of Clb5 to be the primary trigger for cell division were not flawed says Wäsch Rather the conclusions drawn from them were incorrect We can

    Original URL path: http://newswire.rockefeller.edu/2002/08/01/what-inspires-yeast-cells-to-divide/ (2016-02-13)
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  • Studies describe key role for a protein in cell division | Newswire
    Cell in August So we wanted to know how PRC1 works and now we ve got a much better idea Scientists have known that PRC1 for Protein Regular of Cytokines 1 is required in yeast plants and humans for linking together the polymers that make up spindles called microtubules in a specific orientation However how PRC1 mediates microtubule binding and crosslinking was poorly understood Subramanian a postdoctoral fellow in Tarun Kapoor s Laboratory of Chemistry and Cell Biology worked with Seth Darst s Laboratory of Molecular Biophysics to solve the atomic structure of the portion of PRC1 that interacts with microtubules using X ray crystallography The researchers determined that PRC1 binds microtubules through a domain which includes a structure called a spectrin fold This is surprising the scientists say because it s a new role for the spectrin fold which has not been previously shown to mediate microtubule interactions Going further the scientists in collaboration with the laboratory of Ronald Milligan at the Scripps Institute used electron microscopy to determine the structure of pairs of microtubules crosslinked by PRC1 A high resolution image revealed a defined crossbridge conformation of PRC1 which is attained only when the crosslinker is interacting with two microtubules These structural features provide a model for how PRC1 achieves specific crosslinking of antiparallel microtubules PRC1 is a nonmotor protein meaning it does not actively drive microtubules around the cell but rather organizes their structure Another family of proteins motor proteins do the moving Subramanian and her colleagues set up an in vitro fluorescence microscopy based assay in which they could observe PRC1 activity as well as that of a motor protein on the same microtubule pair and found that PRC1 did not interfere with microtubule movements driven by motor proteins So it doesn t act as a

    Original URL path: http://newswire.rockefeller.edu/2010/12/20/studies-describe-key-role-for-a-protein-in-cell-division/ (2016-02-13)
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  • Radhika Subramanian | Newswire
    how one protein PRC1 acts in the penultimate stage of cell division to help form the architectural structures called central spindles needed before the cell can split in two More Tags Laboratory of Chemistry and Cell Biology Radhika Subramanian Seth Darst Tarun Kapoor Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011 more About Contact Follow rockefelleruniv Like The

    Original URL path: http://newswire.rockefeller.edu/tag/radhika-subramanian/ (2016-02-13)
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  • Measuring the strength needed to move chromosomes | Newswire
    a trick but it works out You can catch the spindles says Tarun Kapoor head of the Laboratory of Chemistry and Cell Biology at Rockefeller Now we ve probed the mechanical architecture of the structure as a whole To capture and manipulate the spindles Kapoor and colleagues developed a system of two tiny plate like cantilevers mounted underneath the lens of a microscope that can be maneuvered with micromanipulators to sandwich the elusive structures One of the cantilevers is stiff the other is an ultra thin sensor called a piezo resistive strain sensor that measures the spindle s response to forces when the distance between the two cantilevers is reduced to compress the spindle During cell division meiotic spindles tease apart chromosomes to opposite ends of a cell and ensure that each daughter cell inherits the correct genetic information Scientists have studied many biochemical interactions required for chromosome segregation but know much less about its mechanical properties the actual forces exerted on and by the players involved Kapoor and colleagues determined that the forces strong enough to bend but not break meiotic spindles were in the nanoNewton range about one billionth of the force of Earth s gravity on an average sized apple Applying these minute forces to meiotic spindles assembled in extracts prepared from eggs of African clawed frogs a model system for this kind of research Kapoor found to his surprise that the size of the spindles was not fixed After a series of compressions they readjusted becoming smaller but keeping both the same ratio of length to width roughly two to one and the same strength constant Our immediate goal now is to find out how and why the structure can maintain different sizes This force measuring system could be applied to study cellular organelles and structures

    Original URL path: http://newswire.rockefeller.edu/2009/03/11/measuring-the-strength-needed-to-move-chromosomes/ (2016-02-13)
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  • chromosome segregation | Newswire
    Researchers have used biochemical experiments to study it extensively but until now no one has been able to examine its mechanical properties Rockefeller University professor Tarun Kapoor and colleagues have devised a system to probe these microscopic spindles and have used it for the first time to measure the structure s stiffness and deformability More Tags chromosome segregation Tarun Kapoor Search for Categories Science News Awards and Honors Campus News

    Original URL path: http://newswire.rockefeller.edu/tag/chromosome-segregation/ (2016-02-13)
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