Search results for "Kinetochore"
showing 6 items of 6 documents
Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
2021
The centromere is a fundamental chromosome structure in which the macro-molecular kinetochore assembles and is bound by spindle microtubules, allowing the segregation of sister chromatids during mitosis. Any alterations in kinetochore assembly or functioning or kinetochore–microtubule attachments jeopardize chromosome stability, leading to aneuploidy, a common feature of cancer cells. The spindle assembly checkpoint (SAC) supervises this process, ensuring a faithful segregation of chromosomes. CENP-E is both a protein of the kinetochore and a crucial component of the SAC required for kinetochore–microtubule capture and stable attachment, as well as congression of chromosomes to the metaphas…
Expression of the kinetochore protein Hec1 during the cell cycle in normal and cancer cells and its regulation by the pRb pathway.
2010
Highly Expressed in Cancer protein 1 (Hec1) is a subunit of the Ndc80 complex, a constituent of the mitotic kinetochore. HEC1 has been shown to be overexpressed in many cancers, suggesting that HEC1 upregulation is involved in the generation and/or maintenance of the tumour phenotype. However, the regulation of Hec1 expression in normal and tumour cells and the molecular alterations promoting accumulation of this protein in cancer cells are still unknown. Here we show that elevated Hec1 protein levels are characteristic of transformed cell lines of different origins and that kinetochore recruitment of this protein is also increased in cancer cell lines in comparison with normal human cells.…
Treatment with the anti-tumor drugs, cis-platin and mafosfamide, does not affect the structure of prekinetochores in a human breast cancer cell line.…
1996
Abstract The goal of the present article was to determine whether a nuclear parameter, centromere structure of interphase cells, could serve as an indicator to assess cellular damage caused by anti-tumor drugs. These were cis-platin and mafosfamide, which are widely used for the management of solid tumors. To visualize the centromeres, we probed treated and untreated cells of a human breast cancer cell line, MX-1, with a human anti-centromere serum. The serum was obtained from a scleroderma patient and detects antigens associated with prekinetochores of the decondensed chromosomes. The DNA was simultaneously displayed by a specific fluorescent dye. The cells were grown on coverslips, incuba…
CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly
2016
SummaryHuman centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation. Without the continuing presence of CENP-A, CENP-B binding …
Microtubule organization and distribution of gamma-tubulin in male meiosis of lepidoptera
1996
Meiotic spindles in males of higher Lepidotera are unusual in that the bulk of the spindle micro-tubules (MTs) ends about halfway between the equatorial plate and the centrosomes in metaphase. It appears worthwhile to determine how the MTs are nucleated, while their pole proximal ends are distant from the centrosomes. To this end, spermatocytes of Phragmatobia fuliginosa (Arctiidae), collected in the field, were double-labeled with antibodies to beta- and gamma-tubulin. The former antibody reveals the entire microtubular cytoskeleton, and the latter is directed against a newly-discovered tublin isoform that is prevalent in microtubule-organizing centers (MTOCs). The immunocytochemical work …
An Attachment-Independent Biochemical Timer of the Spindle Assembly Checkpoint.
2017
The spindle assembly checkpoint (SAC) generates a diffusible protein complex that prevents anaphase until all chromosomes are properly attached to spindle microtubules. A key step in SAC initiation is the recruitment of MAD1 to kinetochores, which is generally thought to be governed by the microtubule-kinetochore (MT-KT) attachment status. However, we demonstrate that the recruitment of MAD1 via BUB1, a conserved kinetochore receptor, is not affected by MT-KT interactions in human cells. Instead, BUB1:MAD1 interaction depends on BUB1 phosphorylation, which is controlled by a biochemical timer that integrates counteracting kinase and phosphatase effects on BUB1 into a pulse-generating incohe…