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Department of Biology, Johns Hopkins University, Baltimore, MD 21218

Address correspondence to Trina A. Schroer, Department of Biology/220A Mudd Hall, Johns Hopkins University, Charles and 34th Streets, Baltimore, MD 21218. Tel.: (410) 516-5373. Fax: (410) 516-5375. E-mail: schroer{at}jhu.edu

Centrosomal dynactin is required for normal microtubule anchoring and/or focusing independently of dynein. Dynactin is present at centrosomes throughout interphase, but dynein accumulates only during S and G₂ phases. Blocking dynein-based motility prevents recruitment of dynactin and dynein to centrosomes and destabilizes both centrosomes and the microtubule array, interfering with cell cycle progression during mitosis. Destabilization of the centrosomal pool of dynactin does not inhibit dynein-based motility or dynein recruitment to centrosomes, but instead causes abnormal G₁ centriole separation and delayed entry into S phase. The correct balance of centrosome-associated dynactin subunits is apparently important for satisfaction of the cell cycle mechanism that monitors centrosome integrity before centrosome duplication and ultimately governs the G₁ to S transition. Our results suggest that, in addition to functioning as a microtubule anchor, dynactin contributes to the recruitment of important cell cycle regulators to centrosomes.

Key Words: dynactin; dynein; microtubule; cell cycle; centrosome

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