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DNA loops generate intracentromere tension in mitosis
Authors:Josh Lawrimore  Paula A Vasquez  Michael R Falvo  Russell M Taylor  II  Leandra Vicci  Elaine Yeh  M Gregory Forest  Kerry Bloom
Institution:1.Department of Biology, University of North Carolina, Chapel Hill, NC 27599;2.Department of Physics and Astronomy, University of North Carolina, Chapel Hill, NC 27599;3.Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599;4.Department of Mathematics and Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599;5.Department of Mathematics, University of South Carolina, Columbia, SC 29208
Abstract:The centromere is the DNA locus that dictates kinetochore formation and is visibly apparent as heterochromatin that bridges sister kinetochores in metaphase. Sister centromeres are compacted and held together by cohesin, condensin, and topoisomerase-mediated entanglements until all sister chromosomes bi-orient along the spindle apparatus. The establishment of tension between sister chromatids is essential for quenching a checkpoint kinase signal generated from kinetochores lacking microtubule attachment or tension. How the centromere chromatin spring is organized and functions as a tensiometer is largely unexplored. We have discovered that centromere chromatin loops generate an extensional/poleward force sufficient to release nucleosomes proximal to the spindle axis. This study describes how the physical consequences of DNA looping directly underlie the biological mechanism for sister centromere separation and the spring-like properties of the centromere in mitosis.
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