Kinetochore

Kinetochore

The Kinetochore is the protein structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart.

The kinetochore forms in eukaryotes, assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis.

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

The Kinetochore contains two regions:

• an inner kinetochore, which is tightly associated with the centromere DNA, assembled in a specialized form of chromatin persistent throughout the cell cycle;
• an outer kinetochore, which interacts with microtubules; the outer kinetochore is a very dynamic structure, with many identical components, which are assembled and functional only during cell division.

Kinetochores start, control and supervise the striking movements of chromosomes during cell division. During mitosis, which occurs after chromosomes are duplicated during S phase, two sister chromatids are held together each with its own kinetochore which face in opposing directions and attach to opposite poles of the mitotic spindle. 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. Thus, the kinetochore is essential for the chromosome segregation that is classically associated with mitosis and meiosis.

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 attach 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.

In summary, kinetochore functions include anchoring of chromosomes to MTs in the spindle, verification of anchoring, activation of the spindle checkpoint and participation in force generation to propel chromosome movement during cell division.

On the other hand, MTs 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.