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Phospho-regulation of DDA3 function in mitosis
Authors:Chang-Young Jang  Judith A Coppinger  Guowei Fang
Institution:a Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA
b Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
c Genentech, Inc., South San Francisco, CA 94080, USA
Abstract:DDA3 is a microtubule-associated protein that controls chromosome congression and segregation by regulating the mitotic spindle. Depletion of DDA3 alters spindle structure, generates unaligned chromosomes at metaphase, and delays the mitotic progression. Through a mass spectrometry analysis, we found that DDA3 is phosphorylated on Ser225 during mitosis. Phosphorylation of this residue is important for the mitotic function of DDA3, as the phospho-mimicking DDA3-S225D variant, but not the nonphosphorable DDA3-S225A mutant, rescues the DDA3-knockdown phenotype. We conclude that the mitotic function of DDA3 is regulated by phosphorylation on the Ser225 residue.
Keywords:DDA3  Phosphorylation  Spindle  Chromosome congression  Mitosis
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