The Kinetochore of Mammalian Chromosomes: Structure and Function in Normal Mitosis and Aneuploidy

Brinkley, B. R.; Tousson, Albert; Valdivia, Manuel M.

doi:10.1007/978-1-4613-2127-9_16

Cited by 51 publications

(28 citation statements)

References 36 publications

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“…There is, however, surprising variation in the molecular composition and structural design of kinetochores in eukaryotic cells (for review, see ref. 2). The centromeric DNA sequences identified in the budding yeast Saccharomyces cerevisiae display little homology to those of the fission yeast Schizosaccharomyces pombe (for review, see ref.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies from a patient with scleroderma CREST recognized kinetochores of the higher plant Haemanthus.

Molè-Bajer

Bajer

Zinkowski

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Human autoantibodies from a patient with scleroderma CREST (calcinosis, Raynaud phenomenon, esophageal dismotility, scierodactyly, telangiectasia) were used to immunostain kinetochores on chromosomes in endosperm of the seed of the monocot Haemanthus katherinae Bak. Kinetochores of mitotic chromosomes and prekinetochores of interphase cells were specifically stained using conventional indirect immunofluorescence procedures as well as a nonfading immunogold-silver-enhanced technique and analyzed by fluorescence and video microscopy. In interphase, prekinetochores were either single or double structures depending on the stage of the cell cycle but became quadruple (two distinct stained dots on each chromatid) in mid-to-late prophase. In favorable preparations ofprometaphase chromosomes, multiple subunits could be resolved within each sister kinetochore suggesting a compound organization. Western blot analysis demonstrated common epitopes in centromeric peptides of HeLa and Haemanthus cell extracts. Although the molecular mass of individual polypeptides differed in the two species, the presence of shared epitopes indicates striking conservation of centromere/ kinetochore components throughout evolution.The centromere is a specialized domain located at the primary constriction of most eukaryotic chromosomes and is intimately involved in chromosome segregation (for review, see refs. 1 and 2). The spindle fibers (microtubule bundle), which are instrumental for chromosome segregation, associate with a localized segment of the centromere called the kinetochore. The centromere and kinetochore in some plant and animal cells may not be localized at a single focus, instead being diffuse or polycentric in its distribution along the chromosome. Chromosomes lacking functional kinetochores fail to undergo normal movement and are excluded from the telophase nucleus, often forming micronuclei. Structural rearrangements leading to the formation of two centromeres on the same chromosome (dicentrics) are unstable, resulting in an anaphase bridge, breakage, and fusion cycle (3).Studies of mammalian centromeres/kinetochores have provided the most detailed information on kinetochore structure, composition, and function. The typical mammalian centromere remains unseparated until the onset of anaphase and the kinetochore has a characteristic trilaminar structure with microtubules generally attached to outer-most layer (for review, see refs. 1 and 2).The discovery that human autoantibodies from patients with the CREST (calcinosis, Raynaud phenomenon, esophageal dismotility, sclerodactyly, telangiectasia) variant of scleroderma react with the kinetochore (4-7) and recognize a small family of centromeric proteins (6,8,9) has facilitated the biochemical dissection of this segment of the mammalian chromosome. Moreover, CREST autoantibodies are useful immunostaining reagents because they recognize inactive kinetochores in interphase nuclei (prekinetochores) as well as functional kinetochores on mitotic chromosomes (5). Although anti-ki...

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Section: Discussionmentioning

confidence: 99%

Autoantibodies from a patient with scleroderma CREST recognized kinetochores of the higher plant Haemanthus.

Molè-Bajer

Bajer

Zinkowski

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…The term "ball in a cup" has been used to describe the plant kinetochore, with the emphasis being more on the "cup" of chromatin than the "ball" within (Bajer and Mole-Bajer, 1972). By contrast, animal kinetochores are quite striking when observed in the electron microscope (Brinkley et al, 1989). They are often regarded as having four domains, three discrete layers each defined by differing electron density, and a fibrous corona extending away from the kinetochore.…”

confidence: 99%

The simple ultrastructure of the maize kinetochore fits a two-domain model

Dawe

Richardson

Zhang

2005

Cytogenet Genome Res

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Light microscope observations suggest there are two discrete biochemical domains in the plant kinetochore, an inner domain containing structural proteins, and an outer domain containing proteins involved in motility. We analyzed the ultrastructure of maize meiotic kinetochores following high pressure freezing and freeze substitution, a method that provides excellent sample preservation. Data from meiosis II support previous descriptions of plant kinetochores as diffuse, nearly invisible domains, sometimes nesting in a cup of darkly staining chromatin. The ultrastructure is similar in meiosis I but there are two sister kinetochores that each protrude away from the chromosome and form their own distinct kinetochore fibers. Microtubules terminate within kinetochores where their ends are splayed in a cone-shaped configuration suggestive of microtubule disassembly. We could not detect any significant substructure within the kinetochore proper. We suggest that the diffuse structure classically defined as the kinetochore represents only the outer domain of a two-domain organelle. The inner domain, known to contain chromatin-binding proteins, probably extends into the electron-dense chromatin of the primary constriction.

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“…A specific trilaminar disk-shaped structure, a kinetochore, is formed on the surfaces of the centromeres of mammalian chromosomes during mitosis, and serves as the site of attachment for spindle microtubules (Brinkley et al 1989;Pluta et al 1990;Willard 1990). Chromosomal movement during mitosis has been precisely examined in terms of the interaction between the kinetochore and spindle microtubules at morphological and mechanochemical levels (Kirschner & Mitchison 1986;Rieder et al 1995;Heald et al 1997).…”

Section: Introductionmentioning

confidence: 99%

In vitro assembly of the CENP‐B/α‐satellite DNA/core histone complex: CENP‐B causes nucleosome positioning

et al. 1998

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The Kinetochore of Mammalian Chromosomes: Structure and Function in Normal Mitosis and Aneuploidy

Cited by 51 publications

References 36 publications

Autoantibodies from a patient with scleroderma CREST recognized kinetochores of the higher plant Haemanthus.

Autoantibodies from a patient with scleroderma CREST recognized kinetochores of the higher plant Haemanthus.

The simple ultrastructure of the maize kinetochore fits a two-domain model

In vitro assembly of the CENP‐B/α‐satellite DNA/core histone complex: CENP‐B causes nucleosome positioning

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