Kinetochores maintain a mechanical grip on disassembling microtubule plus ends, possibly through a 16-member Dam1 ring that acts as a sliding clamp. It turns out, however, that a ring is not required for maintaining grip: individual Dam1 complexes in vitro can diffuse on the microtubule lattice and track shortening microtubule tips.
[Show abstract][Hide abstract] ABSTRACT: Accurate chromosome segregation during mitotic division of budding yeast depends on the multiprotein kinetochore complex, Dam1 (also known as DASH). Purified Dam1 heterodecamers encircle microtubules (MTs) to form rings that can function as "couplers," molecular devices that transduce energy from MT disassembly into the motion of a cargo. Here we show that MT depolymerization develops a force against a Dam1 ring that is sixfold larger than the force exerted on a coupler that binds only one side of an MT. Wild-type rings slow depolymerization fourfold, but rings that include a mutant Dam1p with truncated C terminus slow depolymerization less, consistent with the idea that this tail is part of a strong bond between rings and MTs. A molecular-mechanical model for Dam1-MT interaction predicts that binding between this flexible tail and the MT wall should cause a Dam1 ring to wobble, and Fourier analysis of moving, ring-attached beads corroborates this prediction. Comparison of the forces generated against wild-type and mutant complexes confirms the importance of tight Dam1-MT association for processive cargo movement under load.
Proceedings of the National Academy of Sciences 11/2008; 105(40):15423-8. DOI:10.1073/pnas.0807859105 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The highly orchestrated movements of chromosomes during mitosis depend on the formation of stable connections between microtubules and kinetochores. How kinetochores generate these linkages to harness the forces produced by dynamic microtubule plus-ends remains unknown. Three recent studies make significant progress on this front, by identifying a third component of the kinetochore-associated Ska (spindle and kinetochore associated) complex and demonstrating that the complex is required to generate stable kinetochore-microtubule attachments during mitosis in human cells.
The EMBO Journal 06/2009; 28(10):1375-7. DOI:10.1038/emboj.2009.124 · 10.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microtubules are hollow tubes some 25 nm in diameter participating in the eukaryotic cytoskeleton. They are built from alphabeta-tubulin heterodimers that associate to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. The alpha- and beta-tubulins are highly conserved. A third member of the tubulin family, gamma-tubulin, plays a role in microtubule nucleation and assembly. Other members of the tubulin family appear to be involved in microtubule nucleation. Microtubule assembly is accompanied by hydrolysis of GTP associated with beta-tubulin so that microtubules consist principally of 'GDP-tubulin' stabilized at the plus end by a short 'cap'. An important property of microtubules is dynamic instability characterized by growth randomly interrupted by pauses and shrinkage. Many proteins interact with microtubules within the cell and are involved in essential functions such as microtubule growth, stabilization, destabilization, and interactions with chromosomes during cell division. The motor proteins kinesin and dynein use microtubules as pathways for transport and are also involved in cell division. Crystallography and electron microscopy are providing a structural basis for understanding the interactions of microtubules with antimitotic drugs, with motor proteins and with plus end tracking proteins.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.