Unattached kinetochores first bind to a MAD1-C-MAD2-p31 < sup > comet </ sup > complex and releases the p31 < sup > comet </ sup > through unknown mechanisms.

He was elected a member of the French Académie des Beaux-Arts on November 12, 2008, in the " Unattached members " section ( Membres libres ), at the seat formerly held by Marcel Marceau, Seat # 1.

Five years later the National Association of Youth Clubs ( now UK Youth ) published a report called The Unattached about experimental street projects that were taking place up and down the country.

Unattached specimens ( maerl, rhodoliths ) may form relatively smooth compact balls to warty or fruticose thalli.

Unattached, formless and witness of all are you.

He was gazetted a second lieutenant on the Unattached List in January 1901, before being attached to the Royal Dublin Fusiliers.

The FIEC was formed in 1922 under the name A Fellowship of Undenominational and Unattached Churches and Missions, but was later renamed The Fellowship of Independent Evangelical Churches.

Silver Medal: “ Unattached ”, J. J. Adler --- Columbia University.

Unattached to the cable, Starclimber has no way to contact the ground, and is slowly losing power.

However, the primary event associated to the kinetochore attachment to the spindle, which is able to inactivate the inhibitory signal and release the metaphase arrest, could be either the acquisition of microtubules by the kinetochore ( as proposed by Rieder and collaborators in 1995 ), or the tension stabilizing the anchoring of microtubules to the kinetochores ( as suggested by the experiments realized at Nicklas ' lab ).

At metaphase, CENP-E, Bub3 and Bub1 levels disminish about 3 to 4x as compared to free kinetochores, whereas dynein / dynactin, Mad1, Mad2 and BubR1 levels are reduced > 10-100x.

At metaphase, CENP-E, Bub3 and Bub1 levels decreases 3 to 4 fold as compared to the levels at unattached kinetochores, whereas the levels of dynein / dynactin, Mad1, Mad2 and BubR1 decrease > 10-100 fold.

Depolymerization of microtubules generates tension at kinetochores ; bipolar attachment of sister kinetochores to microtubules emanating from opposite cell poles couples opposing tension forces, aligning chromosomes at the cell equator and poising them for segregation to daughter cells.

Although it remains unclear how CLIP170 recognizes plus-ends, it has been shown that its homologues protect against catastrophe and promote rescue, suggesting a role for CLIP170 in stabilizing plus-ends and possibly mediating their direct attachment to kinetochores.

Apc15 mediates the turnover of Cdc20 and MCCs to provide information on the attachment state of kinetochores.

The absence of microtubule attachment to kinetochores activates the spindle assembly checkpoint, causing the cell to arrest in prometaphase.

During prometaphase, CDC20 and the SAC proteins concentrate at the kinetochores before attachment to the spindle assembly.

In response to incorrect kinetochore attachments such as syntelic attachment, where both kinetochores becomes attached to one spindle pole, the weak tension generated destabilizes the incorrect attachment and allows the kinetochore to reattach correctly to the spindle body.

Upon microtubule-kinetochore attachment, a mechanism of stripping via a dynein-dynein motor complex transports spindle checkpoint proteins away from the kinetochores.

Other proteins, such as MAD2 monitor the microtubule attachment as well as the tension between sister kinetochores and activate the spindle checkpoint to arrest the cell cycle when either of these is absent.

These experiments also showed that kinetochores have polarity, and that kinetochore attachment to MTs emanating from one or the other centrosome will depend on its orientation.

Merotelic orientation ( characterized by the absence of tension between sister kinetochores ) is frequent at the beginning of mitosis, but the protein Aurora B ( a kinase conserved from yeast to vertebrates ) detects and eliminates this type of anchoring.

In this direction, Orc2 ( one protein included in the origin recognition complex, ORC, implicated in the initiation of DNA replication during S phase ) is also located on kinetochores during mitosis in human cells ; in agreement with this localization, some observations indicate that Orc2 in yeast is implicated in sister chromatid cohesion, and its removal induces SAC activation.

* Whereas the spindle checkpoint protein levels present in the outer plate diminish as MTs anchor, other components such as EB1, APC and proteins in the Ran pathway ( RanGap1 and RanBP2 ) associate to kinetochores only when MTs are anchored.

This movement is probably mediated by the motor activity towards the " minus " (-) of the motor protein cytoplasmic dynein, which is very concentrated in the kinetochores not anchored to MTs ( reviewed by Banks and Heald in 2001 ).

Another motor protein implicated in the initial capture of MTs is CENP-E ; this is a high molecular weight kinesin associated with the fibrous corona at mammalian kinetochores from prometaphase until anaphase.

In cells with low levels of CENP-E, chromosomes lack this protein at their kinetochores, which quite often are defective in their ability to congress at the metaphase plate.

On the other hand, Dasso and collaborators have found that proteins involved in the Ran cycle can be detected on kinetochores during mitosis: RanGAP1 ( a GTPase activating protein which stimulates the conversion of Ran-GTP in Ran-GDP ) and the Ran binding protein called RanBP2 / Nup358.

Curiously, Orc2 ( a protein that belongs to the origin recognition complex-ORC-implicated in DNA replication initiation during S phase ) is also localized at kinetochores during mitosis in human cells ; in agreement with this localization, some studies indicate that Orc2 in yeast is implicated in sister chromatids cohesion, and when it is eliminated from the cell, spindle checkpoint activation ensues.

** The first one includes the protein adenomatous polyposis coli ( APC ) and the associated protein EB1, which need MTs to localize on the kinetochores.

Furthermore, depletions of various SAC proteins have revealed that MAD2 and BUBR1 depletions affect the timing of mitosis independently of kinetochores, while depletions of other SAC proteins result in a dysfunctional SAC without altering the duration of mitosis.

Thus it is possible that the SAC functions through a two-stage timer where MAD2 and BUBR1 control the duration of mitosis in the first stage, which may be extended in the second stage if there are unattached kinetochores as well as other SAC proteins.

MAD1 localizes to unattached kinetochores while binding strongly to MAD2.

As kinetochore microtubules from both centrioles attach to their respective kinetochores, the homologous chromosomes align along an equatorial plane that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by the microtubules emanating from the two kinetochores of homologous chromosomes.

Attachment of microtubules to chromosomes is mediated by kinetochores, which actively monitor spindle formation and prevent premature anaphase onset.

The growing ends of microtubules are protected against catastrophe by the action of plus-end microtubule tracking proteins (+ TIPs ) to promote their association with kinetochores at the midzone.

On the left is the conventional search-and-capture model in which microtubules emanating from microtubule organizing complexes undergo repeated growth and catastrophe until they bind and are stabilized by kinetochores.

Constrained by cellular dimensions, lateral associations with antiparallel microtubules via motor proteins, and end-on attachments to kinetochores, microtubules naturally adopt a spindle-like structure with chromosomes aligned along the cell equator.

Classic experiments by Rebecca Heald show that functional mitotic spindles and nuclei form around DNA-coated beads incubated in Xenopus egg extracts and that bipolar arrays of microtubules are formed in the absence of kinetochores and MTOCs.

Preceded by events in prometaphase and followed by anaphase, microtubules formed in prophase have already found and attached themselves to kinetochores in metaphase.

This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochores, analogous to a tug-of-war between equally strong people, ending with the destruction of cyclin.

Occasionally, one of the two sister kinetochores may attach simultaneously to MTs generated by both poles, a configuration named merotelic, which is not detected by the spindle checkpoint but that may generate lagging chromosomes during anaphase and, consequently, aneuploidy.

Subsequent studies in cells containing two independent mitotic spindles in a sole cytoplasm showed that the inhibitor of the metaphase-to-anaphase transition is generated by unattached kinetochores and is not freely diffusible in the cytoplasm.

Centromeric cohesion resists the forces exerted by spindle microtubules towards the poles, which generate tension between sister kinetochores.

The beginning of metaphase is characterized by the connection of the microtubules to the kinetochores of the chromosomes, as well as the alignment of the chromosomes in the middle of the cell.

The spindle assembly checkpoint ( SAC ) is an active signal produced by improperly attached kinetochores, which is conserved in all eukaryotes.

In one model, unattached prometaphase kinetochores can ' sensitize ' APC to inhibition of MCC by recruiting the APC to kinetochores via a functioning SAC.

Thus, unattached kinetochores maintain the checkpoint by continuously recreating the MAD2-CDC20 subcomplex from its components.

These early kinetochores show a mature laminar structure before the nuclear envelope breaks down ( reviewed by Pluta et al.