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  • Clearing jams in the copy machinery | Newswire
    replication in the face of DNA damage The replication machinery inside the cell s nucleus is made up of a collection of enzymes including DNA polymerases sliding clamps and clamp loaders Bacteria have five known DNA polymerases higher organisms such as humans have more As the ring shaped beta sliding clamp works its way along the DNA double helix a network of proteins work together to unwind the two strands Polymerases then add in assembly line fashion nucleotide bases the building blocks that make up DNA to convert the now single stranded templates into two new duplex DNA molecules The new research shows that two different DNA polymerases the high fidelity Pol III replicase and the low fidelity Pol IV coordinate their action to cross obstacles encountered in the replication process They attach themselves at the same time to one beta sliding clamp Pol III copies the original DNA and acts as a proofreader to catch any misspellings and cuts any base that is wrong But Pol III is a perfectionist and can stall if it encounters a problem Pol IV on the other hand lays down bases without checking for errors keeping the process moving even when Pol III gets stuck The findings by O Donnell and his colleagues show that because both polymerases are bound simultaneously to the beta clamp it can pull either of the polymerases out if its toolbelt as needed O Donnell and his colleagues propose two explanations for how the polymerase switch is controlled One possibility is that the beta clamp may sense when Pol III stalls triggering a change in beta that pulls the polymerase from the primed site allowing Pol IV to take over synthesis O Donnell says Or Pol III upon stalling may loosen its grip on the template and allow

    Original URL path: http://newswire.rockefeller.edu/2005/09/19/clearing-jams-in-the-copy-machinery/ (2016-02-13)
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  • Rockefeller researchers identify new role for key protein that regulates separation of DNA in dividing cells | Newswire
    each daughter cell receives exactly one copy of each replicated chromosome When errors in this process occur the daughter cells don t receive all their genes leading to developmental defects and diseases such as cancer in the organism One such error occurs when both sister chromosomes of a replicated pair attach to the same pole of the mitotic spindle in a dividing cell The result is that both sister chromosomes are pulled in the same direction leading to an extra copy of a chromosome in one daughter cell and a missing chromosome in the other daughter cell The dividing cell uses two strategies to ensure that each daughter cell receives its full complement of genes One such strategy involves regulating the attachments of chromosomes to each of the spindle poles which Lampson and Kapoor showed in a 2004 paper in Nature Cell Biology is performed by an enzyme called Aurora kinase The other strategy is to delay the onset of a stage of the cell cycle called anaphase until all the attachments are correctly made Once a cell goes into anaphase there is no going back says Lampson a postdoctoral researcher in the Laboratory of Chemistry and Cell Biology headed by Kapoor It s an irreversible step A process called the mitotic checkpoint monitors the attachment process and if it detects incorrect attachments delays anaphase This essentially allows the attachment machinery to correct any flawed attachments before the cell goes into anaphase Once all the attachments are correctly made the checkpoint shuts down and the cell cycle proceeds The question Lampson and Kapoor wanted to answer was How are the two strategies coordinated Lampson used a technique called RNA interference to knock down three proteins BubR1 CENP E and Mad2 in laboratory cultures of human cells BubR1 and Mad2 have

    Original URL path: http://newswire.rockefeller.edu/2005/01/26/rockefeller-researchers-identify-new-role-for-key-protein-that-regulates-separation-of-dna-in-dividing-cells/ (2016-02-13)
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  • Four Rockefeller scientists elected to the National Academy of Sciences | Newswire
    an official advisor to the federal government upon request in any matter of science or technology Today s election brings the total number of Rockefeller University faculty who are members or foreign associates of the Academy to 36 de Lange was elected as one of 18 foreign associates nonvoting members with citizenship outside the United States de Lange is Leon Hess Professor and head of the Laboratory of Cell Biology and Genetics She studies how loops of DNA protein complexes at the ends of human chromosomes called telomeres protect chromosome ends and mediate their replication Her research is aimed at determining how cells distinguish natural chromosome ends from accidental breaks in DNA and what happens when telomere protection is lost Gilbert Arthur and Janet Ross Professor and head of the Laboratory of Neurobiology studies the mechanisms underlying visual perception including the role of the brain s visual cortex in analyzing visual images and in perceptual learning His lab aims to understand the mechanisms of sensory processing in the cortex by working at the interface of microcircuitry receptive field properties and functional architecture and to establish the relationship between the operation of neuronal ensembles and perceptual performance O Donnell professor and head of the Laboratory of DNA Replication is also an investigator at the Howard Hughes Medical Institute His laboratory studies DNA replication mechanisms in cells and his goal is to achieve an understanding in mechanical detail of how the numerous protein gears act together to duplicate DNA and how they function with repair and recombination factors as well Ravetch who is Theresa and Eugene M Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology focuses on dissecting the cellular and molecular mechanisms governing the generation of specific immune system antibodies His work seeks to identify

    Original URL path: http://newswire.rockefeller.edu/2006/04/26/four-rockefeller-scientists-elected-to-the-national-academy-of-sciences/ (2016-02-13)
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  • Charles D. Gilbert | Newswire
    modified by experience More Tags Charles D Gilbert Laboratory of Neurobiology April 26 2006 Awards and Honors Four Rockefeller scientists elected to the National Academy of Sciences Titia de Lange Charles D Gilbert Michael E O Donnell and Jeffrey V Ravetch all heads of laboratories at Rockefeller University have been elected to the U S National Academy of Sciences a private organization of scientists and engineers dedicated to the furtherance

    Original URL path: http://newswire.rockefeller.edu/tag/charles-d-gilbert/ (2016-02-13)
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  • Elusive protein points to mechanism behind hearing loss | Newswire
    Laboratory of Sensory Neuroscience and a Howard Hughes Medical Institute investigator didn t detect any structural defects in the zebra fish s inner ear which houses sound sensors called hair cells The cells are adorned with height ordered hair like projections called stereocilia which when deflected toward the tallest member set in motion a series of events that decodes sounds into a neural code It was such a clean phenotype says Gleason Everything about the mutants inner ear seemed normal All ears Electron micrographs of two hair cell bundles in the zebra fish ear show the difference between those born with left and without right the protein Tmie But something was clearly amiss Even though the deaf zebra fish had hair cells several tests used to measure their presence and function made it seem as if these hair cells might as well not be there By comparing the genomes of normal zebra fish and the deaf ones the team mapped the affected DNA and then zeroed in on the precise gene which encodes for the protein Tmie The gene had two mutations resulting in a severely shortened protein that affected the function of the hair like sensors leading to hearing loss Using powerful electron microscopy techniques Gleason and her colleagues confirmed previous findings in mice studies that showed abnormalities in the hair cells The deaf zebra fish had fewer and shorter kinocilia as well as a reduced number of stereocillia But the researchers also found that the tips of the stereocilia were much thinner than normal stereocilia and lacked a tethering protein that connects one stereocilium to the next The findings says Gleason suggest that Tmie plays a bigger role in the transmission of sound than previously thought At the ultra structural level we specifically show that these mutant defects

    Original URL path: http://newswire.rockefeller.edu/2009/12/04/elusive-protein-points-to-mechanism-behind-hearing-loss/ (2016-02-13)
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  • Neuron in zebrafish may reveal clues to the wiring of the human ear | Newswire
    nerve fiber heads straight for its target suggesting the brain takes a hardwired approach to assessing its surroundings That target hair cells sensory cells with discrete bundles of hair like projections called stereocilia which increase in length from one edge of the hair bundle to the other When deflected the stereocilia can detect vanishingly small sounds or motions and the direction in which the stereocilia are deflected determines the response of the hair cell Nagiel and Hudspeth found that nerve fibers coming from the head only form connections with hair cells that detect stimuli coming from the same direction The sister cells are mirror images of each other and somehow they are able to advertise their different polarities says Nagiel The hair cells could be using a chemical cue to tell the neuron We are the right match Specifically Nagiel and Hudspeth studied the zebrafish s posterior lateral line system of cells whose hair like projections are directly exposed to the water and sense its movement The posterior lateral line which runs horizontally from the zebrafish s neck to its tail is dotted with several clusters of hair cells called neuromasts which are distributed in precise locations and contain up to 20 cells each By using live imaging techniques with a confocal microscope and special dyes the researchers found that nerve fibers form connections with many hair cells of the same polarity within one neuromast or several of them But that s not all Before now Nagiel and Hudspeth had shown that neurons and hair cells make contact But we wanted to rigorously show that these contacts were synapses says Nagiel To do so Nagiel and his colleagues constructed a molecule that enabled the team to look at the two cells point of contact underneath an electron microscope a powerful

    Original URL path: http://newswire.rockefeller.edu/2008/09/23/neuron-in-zebrafish-may-reveal-clues-to-the-wiring-of-the-human-ear/ (2016-02-13)
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  • New report bolsters theory on ear’s inner amplifier | Newswire
    within the last 20 years have scientists even been able to confirm that it has its own built in amplifier the cochlea a coiled tube in the inner ear Inside the cochlea lies the basilar membrane which is carpeted with thousands of tiny hair cells that vibrate in response to sound waves magnifying noises Precisely how the hair cells do this however is debatable and two competing theories exist One proposes that the hair cells pump like pistons in response to vibration strengthening the motion of the basilar membrane and creating the amplification effect Hudspeth s theory on the other hand suggests that the hair cells themselves actively enhance the sound Each of these cells has a hair bundle which consists of as many as 300 hair like fibers projecting from its tip When the fibers called steriocilia bend in response to sound the resulting tension unlocks ion channels which open like little trap doors and allow potassium and calcium ions to flow into the cell Hudspeth s theory suggests that once calcium enters the stereocilia the trapdoor snaps shut again and the resulting force is what causes amplification In a quiet environment hair cells spontaneously vibrate and emit sound an action that indicates that something in the ear is indeed acting as an amplifier Hudspeth who is the F M Kirby Professor and also an investigator at the Howard Hughes Medical Institute and his team examined individual hair bundles as they did this using cells from a bullfrog that had been rigged to act as if they were still inside the frog They then took snapshot measurements of the directional force acting on the bundles as they oscillated and found that these measurements were consistent with Hudspeth s ion channel theory The bundles showed distinct changes immediately before the

    Original URL path: http://newswire.rockefeller.edu/2005/11/18/new-report-bolsters-theory-on-ears-inner-amplifier/ (2016-02-13)
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  • cochlea | Newswire
    competing theories exist to explain how the human ear amplifies sound Now using ear hair cells from a bullfrog scientists at Rockefeller provide evidence to bolster the theory they proposed in 1998 More Tags A James Hudspeth cochlea stereocilia 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 Rockefeller University RU Footer

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