Entry into mitosis in vertebrate cells is guarded by a checkpoint that can be activated by a variety of insults, including chromosomal damage and disrupting microtubules. This checkpoint acts at the end of interphase to delay cells from entering mitosis, causing cells in prophase to decondense their chromosomes and return to G2 phase. Here, we show that in response to microtubule poisons this "...

Chromokinesins are microtubule-motor molecules that possess chromatin binding activity and are important for mitotic and meiotic regulation. The chromokinesin-member Kif4A is unique in that it localizes to nucleus during interphase of the cell cycle. Kif4 deletion by gene targeting in mouse embryonic cells was known to associate with DNA damage response. However, its precise role in DNA damage ...

Colorectal cancers commonly carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein contributes to the stabilization of microtubules. Consistently, microtubules in cells lacking APC depolymerize more readily in response to microtubule-destabilizing drugs. This raises the possibility that such agents are suitable for treatment of APC-deficient cancers. However, A...

We have designed experiments that distinguish centrosomal , nuclear, and cytoplasmic contributions to the assembly of the mitotic spindle. Mammalian centrosomes acting as microtubule-organizing centers were assayed by injection into Xenopus eggs either in a metaphase or an interphase state. Injection of partially purified centrosomes into interphase eggs induced the formation of extensive aster...

The sites of microtubule growth and the kinetics of elongation have been studied in vivo by microinjection of biotin-labeled tubulin and subsequent visualization with immunocytochemical probes. Immunofluorescence and immunoelectron microscopy demonstrate that injected biotin-labeled subunits are incorporated into new segments of growth which are contiguous with unlabeled microtubules. Rapid inc...

Cep192 is a centrosomal protein that contributes to the formation and function of the mitotic spindle in mammalian cells. Cep192's mitotic activities stem largely from its role in the recruitment to the centrosome of numerous additional proteins such as gamma-tubulin and Pericentrin. Here, we examine Cep192's function in interphase cells. Our data indicate that, as in mitosis, Cep192 stimulates...

29 Entry into mitosis triggers profound changes in cell shape and cytoskeletal 30 organisation. Here, by studying microtubule remodelling in human flat mitotic cells, 31 we identify a two-step process of interphase microtubule disassembly. First, a 32 microtubule stabilizing protein, Ensconsin, is inactivated in prophase as a 33 consequence of its phosphorylation downstream of Cdk1/CyclinB. Thi...

The microtubules control many cellular functions and play a key role in cell morphogenesis and development. They are dynamic heteropolymers composed of ┙and ┚-tubulin and microtubule associated proteins (MAPs) that bind to microtubules and regulate their polymerization, organization and dynamic behavior. The structure of microtubules and tubulins are almost identical from yeast to human, yet th...

Overexpression of dynein fragments in Dictyostelium induces the movement of the entire interphase microtubule array. Centrosomes in these cells circulate through the cytoplasm at rates between 0.4 and 2.5 microm/s and are trailed by a comet-tail like arrangement of the microtubule array. Previous work suggested that these cells use a dynein-mediated pulling mechanism to generate this dramatic m...

The centrosome serves as the primary micro-tubule-organizing center in animal cells and, consequently, functions in many processes, such as migration and formation of the mitotic spindles. The centrosome consists of a pair of centrioles surrounded by pericentriolar material (PCM), the platform for microtubule nucle-ation. The pair of centrioles duplicate once per cell cycle to ensure the equal ...