A kinetochore is a complex protein structure on chromosomes that serves as the attachment point for spindle microtubules, which pull chromosomes apart. This mechanism is fundamental for ensuring genetic material is accurately distributed during cell division. Without proper kinetochore function, cell division would be severely compromised.
Where Kinetochores Are Found and Their Primary Role
Kinetochores are found on duplicated chromosomes at a constricted region called the centromere. Each duplicated chromosome, composed of two identical sister chromatids, has two kinetochores, one on each chromatid. These protein patches face in opposite directions, preparing for segregation.
The primary function of kinetochores is to serve as the binding site for spindle microtubules. This attachment is observed during mitosis and meiosis, the two primary forms of cell division. Kinetochores facilitate the precise positioning and separation of chromosomes, ensuring each new cell receives a complete and accurate set of genetic information.
The Kinetochore’s Complex Architecture
The kinetochore exhibits a multi-layered protein structure, visible under electron microscopy as a disc-shaped complex. It consists of three main regions: an inner kinetochore, an outer kinetochore, and a fibrous corona. The inner kinetochore is tightly associated with the centromere DNA of the chromosome and remains present throughout the cell cycle.
The outer kinetochore is a dynamic region that becomes functional during cell division. It is the interface that directly interacts with the spindle microtubules. Extending from the outer kinetochore is the fibrous corona, which aids in microtubule capture and anchoring. These layers are composed of numerous proteins, with even the simplest kinetochores containing over 19 different proteins, all working to manage chromosome movement.
How Kinetochores Direct Chromosome Movement
Kinetochores orchestrate chromosome movement through dynamic interactions with spindle microtubules. During metaphase, kinetochores attach to these microtubules, which extend from opposite poles of the cell, generating tension. This tension pulls the sister chromatids in opposing directions, aligning them at the cell’s center, known as the metaphase plate.
Kinetochores also act as molecular motors, utilizing proteins like dynein and kinesin to move along the microtubules. They are capable of sensing mechanical tension, which signals proper attachment. If attachments are incorrect or tension is absent, the kinetochore can activate a “stop signal” through the spindle assembly checkpoint (SAC), delaying cell division until all chromosomes are properly aligned and under tension. This pathway prevents premature separation and safeguards against errors in chromosome distribution.
When Kinetochores Go Wrong
Dysfunction in kinetochores can have severe consequences for cell division and organismal health. Errors in microtubule attachment or a failure to properly sense tension can lead to a condition called aneuploidy. Aneuploidy refers to an abnormal number of chromosomes in a cell, meaning there are either too many or too few chromosomes.
Such errors often arise from issues like merotelic attachments, where a single kinetochore binds to microtubules from both spindle poles, or a complete failure of a kinetochore to attach. Aneuploidy is frequently observed in cancer cells, with about 70% of solid tumors exhibiting this condition. It is also associated with various developmental disorders.