Journal of Cell Science & Therapy
Open Access

Kinetochore Assembly and Function in the Regulation of Mitosis

Jeffrey Saber^{* *}Correspondence: Jeffrey Saber, Department of Molecular Biosciences, Stockholm University, Stockholm, Sweden, Email:

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Description

The kinetochore is a dynamic and essential structure that regulates mitosis, the process by which a eukaryotic cell divides to form two genetically identical daughter cells. The kinetochore, which assembles on the centromere of each chromosome, plays a central role in ensuring that chromosomes are properly attached to the mitotic spindle and segregated accurately into the daughter cells.

Kinetochore

The kinetochore is a complex protein structure composed of multiple layers and subcomponents that function in coordination with other cellular machinery to regulate mitosis. The kinetochore assembles on the centromere region of the chromosome, which serves as the anchor point for both the kinetochore complex and the spindle microtubules. The centromere is typically marked by specialized histone proteins, such as CENP-A, which help facilitate kinetochore formation.

The inner kinetochore proteins interact with the centromeric DNA and provide a foundation for the entire kinetochore structure. Key components include CENP-C and CENP-I, which help stabilize the attachment of the kinetochore to the centromere. The outer kinetochore interacts with the mitotic spindle, specifically with the microtubules that make up the spindle fibers.

One of the primary functions of the kinetochore is to mediate the attachment of chromosomes to the mitotic spindle, which is composed of microtubules. Microtubules are polymerized from the spindle poles, and their plus ends interact with the kinetochore. These microtubules attach to the kinetochore through the Ndc80 complex, which forms a stable connection that enables chromosome movement.

Proper chromosome alignment and tension between the sister chromatids are crucial for accurate segregation. During metaphase, the chromosomes align at the metaphase plate, an equatorial region of the cell. The kinetochore regulates this process by ensuring that each chromosome is attached to microtubules from both spindle poles, which allows for proper tension to be generated across the chromosome. If chromosomes experience insufficient or asymmetric tension, the Spindle Assembly Checkpoint (SAC) is activated to prevent the cell from progressing to anaphase. The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism that ensures that chromosomes are properly attached and aligned before the cell proceeds to anaphase.

These proteins inhibit the Anaphase-Promoting Complex (APC/ C), preventing the onset of anaphase and delaying cell cycle progression. This allows the APC/C to initiate the degradation of securin and cyclin B, triggering the onset of anaphase and the separation of sister chromatids. Separate cleaves cohesin, a protein complex that holds sister chromatids together, allowing the chromatids to separate and be pulled toward opposite poles of the cell. During anaphase, the kinetochore facilitates the movement of chromatids toward the spindle poles. This involves both the microtubule depolymerization at the kinetochore and the sliding of microtubules at the spindle poles. Kinetochore motor proteins, such as CENP-E and Dynein, also contribute to this movement.

Improper attachment of microtubules to the kinetochore can result in misalignment or failure to segregate chromosomes, leading to aneuploidy (abnormal chromosome number). In some cases, the SAC may fail to fully block anaphase progression, even if chromosomes are misaligned, resulting in the premature separation of chromatids. Mutations in kinetochore proteins or the centromeric DNA can also disrupt mitotic progression, leading to improper chromosome segregation and contributing to developmental disorders or cancer.

Conclusion

Kinetochore assembly and its dynamic function in regulating mitosis are critical for the accurate segregation of chromosomes. By mediating microtubule attachment, sensing tension, and ensuring proper alignment through the spindle assembly checkpoint, the kinetochore ensures that each daughter cell receives a complete and accurate set of chromosomes. Disruption in kinetochore function can lead to genomic instability, contributing to diseases such as cancer.