Kinetochore

A kinetochore (/kɪˈnɛtəkɔːr/, /-ˈniːtəkɔːr/) is a flared oblique-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers, which can be thought of as the ropes pulling chromosomes apart, attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore (= movement place) has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

Monocentric organisms, including vertebrates, fungi, and most plants, have a single centromeric region on each chromosome which assembles a single, localized kinetochore. Holocentric organisms, such as nematodes and some plants, assemble a kinetochore along the entire length of a chromosome.

Kinetochores start, control, and supervise the striking movements of chromosomes during cell division. During mitosis, which occurs after the amount of DNA is doubled in each chromosome (while maintaining the same number of chromosomes) in S phase, two sister chromatids are held together by a centromere. Each chromatid has its own kinetochore, which face in opposite directions and attach to opposite poles of the mitotic spindle apparatus. Following the transition from metaphase to anaphase, the sister chromatids separate from each other, and the individual kinetochores on each chromatid drive their movement to the spindle poles that will define the two new daughter cells. The kinetochore is therefore essential for the chromosome segregation that is classically associated with mitosis and meiosis.

The kinetochore contains two regions:

Even the simplest kinetochores consist of more than 19 different proteins. Many of these proteins are conserved between eukaryotic species, including a specialized histone H3 variant (called CENP-A or CenH3) which helps the kinetochore associate with DNA. Other proteins in the kinetochore adhere it to the microtubules (MTs) of the mitotic spindle. There are also motor proteins, including both dynein and kinesin, which generate forces that move chromosomes during mitosis. 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. The actual set of genes essential for kinetochore function varies from one species to another.

Kinetochore functions include anchoring of chromosomes to MTs in the spindle, verification of anchoring, activation of the spindle checkpoint and participation in the generation of force to propel chromosome movement during cell division. On the other hand, microtubules are metastable polymers made of α- and β-tubulin, alternating between growing and shrinking phases, a phenomenon known as dynamic instability. MTs are highly dynamic structures, whose behavior is integrated with kinetochore function to control chromosome movement and segregation. It has also been reported that the kinetochore organization differs between mitosis and meiosis and the integrity of meiotic kinetochore is essential for meiosis specific events such as pairing of homologous chromosomes, sister kinetochore monoorientation, protection of centromeric cohesin and spindle-pole body cohesion and duplication.

The kinetochore is composed of several layers, observed initially by conventional fixation and staining methods of electron microscopy, (reviewed by C. Rieder in 1982) and more recently by rapid freezing and substitution.

The deepest layer in the kinetochore is the inner plate, which is organized on a chromatin structure containing nucleosomes presenting a specialized histone (named CENP-A, which substitutes histone H3 in this region), auxiliary proteins, and DNA. DNA organization in the centromere (satellite DNA) is one of the least understood aspects of vertebrate kinetochores. The inner plate appears like a discrete heterochromatin domain throughout the cell cycle.