The Eukaryotic Chromosome Is a Segregation Device

KEY CONCEPT
A eukaryotic chromosome is held on the mitotic spindle by the attachment of microtubules to the kinetochore that forms in its centromeric region.
During mitosis, the sister chromatids move to opposite poles of the cell. Their movement depends on the attachment of the chromosome to microtubules, which are connected at their other end to the poles. The microtubules comprise a cellular filamentous system, which is reorganized at mitosis so that they connect the chromosomes to the poles of the cell. The sites in the two regions where microtubule ends are organized—in the vicinity of the centrioles at the poles and at the chromosomes—are called microtubule organizing centers (MTOCs).
FIGURE 1 illustrates the separation of sister chromatids as mitosis proceeds from metaphase to telophase. The region of the chromosome that is responsible for its segregation at mitosis and meiosis is called the centromere. The centromeric region on each sister chromatid is moved along microtubules to the opposite pole.
Opposing this motive force, “glue” proteins called cohesins hold the sister chromatids together. Initially the sister chromatids separate at their centromeres, then they are released completely from one another during anaphase when the cohesins are degraded. The centromere is moved toward the pole during mitosis, and the attached chromosome appears to be “dragged along” behind it. The chromosome therefore provides a device for attaching a large number of genes to the apparatus for division.
The centromere essentially acts as the luggage handle for the entire chromosome and its location typically appears as a constricted region connecting all four chromosome arms,  which shows the sister chromatids at the metaphase stage of mitosis.

FIGURE 1 Chromosomes are pulled to the poles via microtubules that attach at the centromeres. The sister chromatids are held together until anaphase by glue proteins (cohesins). The centromere is shown here in the middle of the chromosome (metacentric), but can be located anywhere along its length, including close to the end (acrocentric) and at the end (telocentric).
The centromere is essential for segregation, as shown by the behavior of chromosomes that have been broken. A single break generates one piece that retains the centromere, and another, an acentric fragment, that lacks it. The acentric fragment does not become attached to the mitotic spindle, and as a result it fails to be included in either of the daughter nuclei. When chromosome movement relies on discrete centromeres, there can be only one centromere per chromosome. When translocations generate chromosomes with more than one centromere, aberrant structures form at mitosis. This is because the two centromeres on the same sister chromatid can be pulled toward different poles, thus breaking the chromosome. In some species, though (such as the nematode Caenorhabditis elegans), the centromeres are holocentric, being diffuse and spread along the entire length of the chromosome.
Species with holocentric chromosomes still make spindle fiber attachments for mitotic chromosome separation, but do not require one and only one regional or point centromere per chromosome.
Most of the molecular analysis of centromeres has been done on canonical point (budding yeast) or regional (fly, mammalian, rice) centromeres.
The regions flanking the centromere often are rich in satellite DNA sequences and display a considerable amount of heterochromatin.
The entire chromosome is condensed, though, so centromeric heterochromatin is not immediately evident in mitotic chromosomes.
Researchers can, however, visualize it by a technique that generates “C-bands.” For example, in FIGURE 2 all the centromeres show as darkly staining regions. Although it is common, heterochromatin cannot be identified around every known centromere, which suggests that it is unlikely to be essential for the division mechanism.

FIGURE 2 C-banding generates intense staining at the centromeres of all chromosomes.
Photo courtesy of Lisa Shaffer, Washington State University, Spokane.
The centromeric chromatin comprises DNA sequences, specialized centromeric histone variants, and a group of specific proteins that are responsible for establishing the structure that attaches the chromosome to the microtubules. This structure is called then kinetochore. It is a darkly staining fibrous object of about 400 nm.
The kinetochore provides a microtubule attachment point on the chromosome.