Disease relevance of Kinetochores

• Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110 [1].
• Both a point mutation in the baculovirus IAP repeat motif (C84A) and a COOH-terminal deletion mutant (Delta106) of survivin fail to localize to either kinetochores or midbodies, but neither interferes with cell cleavage [2].
• Several autoimmune sera from patients with Raynaud phenomenon decorated mammalian kinetochores and bound to a 47-kDa protein on immunoblots of nuclear lysates [3].
• Characterisation of centromere (kinetochore) antigen reactive with sera of patients with a scleroderma variant (CREST syndrome) [4].
• Localization of Ca(2+)-calmodulin to the kinetochore of C6 glioma cells: an investigation of the anti-tumour effects of calmodulin antagonists in the treatment of brain tumours [5].

Psychiatry related information on Kinetochores

• An inhibitor study also suggested that the motor activity of dynein is required for the removal of CLIP-190 from attached kinetochores [6].

High impact information on Kinetochores

• Here, we show that CLASP1, a microtubule-associated protein, localizes preferentially near the plus ends of growing spindle microtubules and is also a component of a kinetochore region that we term the outer corona [7].
• One of the most intriguing aspects of mitosis is the ability of kinetochores to hold onto plus ends of microtubules that are actively gaining or losing tubulin subunits [7].
• Kinetochores detach from old SPBs and reattach to old and new SPBs with equal frequency in IPL1+ cells, but remain attached to old SPBs in ipl1 mutants [8].
• This raises the possibility that Ipl1-Sli15 facilitates bi-orientation by promoting turnover of kinetochore-SPB connections until traction of sister kinetochores toward opposite spindle poles creates tension in the surrounding chromatin [8].
• By deleting genes that are upregulated during meiosis, we identified in Saccharomyces cerevisiae a kinetochore associated protein, Mam1 (Monopolin), which is essential for monopolar attachment [9].

Biological context of Kinetochores

• CENP-E is a plus end-directed kinetochore motor required for metaphase chromosome alignment [10].
• We show here that a murine homolog of the yeast mitotic checkpoint gene BUB1 localizes to the kinetochore during mitosis [11].
• Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression [12].
• Regulating the yeast kinetochore by ubiquitin-dependent degradation and Skp1p-mediated phosphorylation [13].
• CTF14 is identical to NDC10/CBF2, a recently identified essential gene that encodes a 110 kd kinetochore component [14].

Anatomical context of Kinetochores

• These findings support a model in which CENP-E functions in congression to tether kinetochores to dynamic microtubule plus ends [10].
• There is also evidence to indicate that the spindle checkpoint components and Cdc20 are spatially regulated by the mitotic apparatus, in particular they are recruited to improperly attached kinetochores [15].
• We mapped distinct domains of Cdc20 that are required for association with kinetochores and centrosomes [16].
• As CENP-E and hBUBR1 can coimmunoprecipitate with each other from HeLa cells, they may function as a motor-kinase complex at kinetochores [17].
• Nup358 integrates nuclear envelope breakdown with kinetochore assembly [18].

Associations of Kinetochores with chemical compounds

• XMAD2 protein associated with unattached kinetochores in prometaphase and in nocodazole-treated cells and disappeared from kinetochores at metaphase in untreated cells, suggesting that XMAD2 plays a role in the activation of the checkpoint by unattached kinetochores [19].
• In leptomycin B-treated cells, centromeres frequently associated with continuous microtubule bundles that spanned the centromeres, indicating that their kinetochores do not maintain discrete end-on attachments to single kinetochore fibres [20].
• ATP, GTP, or ATP-gamma-S added in the PM 4-7 min later restarted anaphase A while kinetochore fibers shortened [21].
• The results indicate that aside from ribosomes, the major RNP-containing components of the spindle are the kinetochores and centrioles, both of which stain electron-opaque after EDTA treatment [22].
• We used a density gradient (metrizamide) to obtain an enriched fraction of stained material (kinetochore) [23].

Gene context of Kinetochores

• In S. cerevisiae, the four-protein Cbf3 complex binds to the essential CDEIII region of centromeric DNA to initiate kinetochore assembly [13].
• Together, the genetic and biochemical data indicate that CTF13 is an essential kinetochore protein [14].
• Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage [11].
• Ask1 localizes along mitotic spindles and to kinetochores, and cross-links to centromeric DNA [24].
• In addition, Ctf3p, Mcm22p, and Mcm16p have a localization pattern similar to other kinetochore proteins [25].

Analytical, diagnostic and therapeutic context of Kinetochores

• Immunofluorescence staining of dynactin and cytoplasmic dynein components in cultured vertebrate cells showed that both complexes are recruited to kinetochores during prometaphase, and concentrate near spindle poles thereafter [26].
• The human autoantigen CENP-C has been demonstrated by immunoelectron microscopy to be a component of the inner kinetochore plate [27].
• DNA mobility-shift assays indicated that the major complex formed between the CENP-B and the DNA contains two DNA molecules, suggesting the importance of the CENP-B/CENP-B box interaction in organization of higher ordered chromatin structures in the centromere and/or kinetochore [28].
• Probing the Saccharomyces cerevisiae centromeric DNA (CEN DNA)-binding factor 3 (CBF3) kinetochore complex by using atomic force microscopy [29].
• Fluorescence light microscopy, live cell imaging, and electron microscopy provide quantitative data demonstrating that Nuf2 and Hec1 are essential for normal kinetochore microtubule attachment [30].

References