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Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase


During anaphase identical sister chromatids separate and move towards opposite poles of the mitotic spindle1,2. In the spindle, kinetochore microtubules3 have their plus ends embedded in the kinetochore and their minus ends at the spindle pole. Two models have been proposed to account for the movement of chromatids during anaphase. In the ‘Pac-Man’ model, kinetochores induce the depolymerization of kinetochore microtubules at their plus ends, which allows chromatids to move towards the pole by ‘chewing up’ microtubule tracks4,5. In the ‘poleward flux’ model, kinetochores anchor kinetochore microtubules and chromatids are pulled towards the poles through the depolymerization of kinetochore microtubules at the minus ends6. Here, we show that two functionally distinct microtubule-destabilizing KinI kinesin enzymes (so named because they possess a kinesin-like ATPase domain positioned internally within the polypeptide) are responsible for normal chromatid-to-pole motion in Drosophila. One of them, KLP59C, is required to depolymerize kinetochore microtubules at their kinetochore-associated plus ends, thereby contributing to chromatid motility through a Pac-Man-based mechanism. The other, KLP10A, is required to depolymerize microtubules at their pole-associated minus ends, thereby moving chromatids by means of poleward flux.

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Figure 1: KLP10A and KLP59C perform distinct functions and localize to distinct sites in mitotic cells.
Figure 2: KLP10A inhibition perturbs mitotic spindle assembly and chromosome segregation.
Figure 3: KLP59C inhibition perturbs chromosome segregation but not spindle assembly.
Figure 4: KLP10A is required for poleward flux whereas KLP59C is required for Pac-Man-based chromosome motility.

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We would like to thank B. Kenigsberg, D. Buster, P. Baas, F. McNally, A. Asenjo and H. Sosa for critically reading the manuscript; I. Brust-Mascher for advice on FSM; and A. Desai and J. Minden for help with rhodamine-histone preparations. We also thank C. Sunkel for providing GFP-Polo kinase flies and protocols for isolating mitotic chromosomes. We are grateful to the following individuals for their gifts: GFP–tubulin flies from A. Spradling; GFP-DTACC flies from J. Raff; GFP–Rod flies from R. Karess; GFP-Cid flies from S. Henikoff; and G. Karpen for the anti-Cid antibody. We thank G. Law, P. Franklin and R. Sleeper (PerkinElmer) for their assistance with the Ultraview confocal microscope. This work was supported by grants from the National Institutes of Health to D.J.S., C.E.W, R.D.V. and J.M.S.. C.E.W is a Scholar of the Leukemia and Lymphoma Society.

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Correspondence to David J. Sharp.

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Supplementary information

Supplementary Figure 1 (PDF 806 kb)

Supplementary Figure 2 (PDF 23 kb)

Supplementary Figure 3 (PDF 65 kb)

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Supplementary Movie 1: 4-D (xyz/time) movie of mitosis in a control-injected syncytial blastoderm-stage embryo expressing GFP-tubulin. (ZIP 1220 kb)

Supplementary Movie 2: 4-D movie showing mitosis in a control-injected embryo containing GFP-histones (green) and rhodamine-tubulin (red). (MOV 1259 kb)

Supplementary Movie 3: 4-D movie from an anti-KLP10A antibody-injected embryo expressing GFP-tubulin. (ZIP 1667 kb)

Supplementary Movie 4: 4-D movie from anti-KLP10A antibody-injected embryo containing GFP-histones (green) and rhodamine-tubulin (red). (MOV 1737 kb)

Supplementary Movie 5: 4-D movie from an anti-KLP59C antibody-injected embryo containing GFP-histones (green) and rhodamine-tubulin (red). (ZIP 1116 kb)

Supplementary Movie 6: FSM movie showing microtubule-behaviors in spindles from a control-injected embryo. (ZIP 1156 kb)

Supplementary Movie 7: FSM movie showing microtubule behaviors in a spindle from an anti-KLP10A antibody-injected embryo. (ZIP 1197 kb)

Supplementary Figure Legends (DOC 46 kb)

Supplementary Movie Legends (DOC 20 kb)

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Rogers, G., Rogers, S., Schwimmer, T. et al. Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase. Nature 427, 364–370 (2004).

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