regulation of kinetochore assembly

Definition

Target type: biologicalprocess

Any process that modulates the rate, frequency, or extent of kinetochore assembly, the aggregation, arrangement and bonding together of a set of components to form the kinetochore, a multisubunit complex that is located at the centromeric region of DNA and provides an attachment point for the spindle microtubules. [GOC:ascb_2009, GOC:dph, GOC:tb]

Regulation of kinetochore assembly is a highly orchestrated process that ensures accurate chromosome segregation during cell division. It involves the precise recruitment and assembly of numerous proteins at the centromere, a specialized DNA region on each chromosome. The kinetochore, a complex protein structure assembled on the centromere, serves as the attachment point for microtubules emanating from the spindle poles, thus mediating chromosome movement.

The process of kinetochore assembly is tightly regulated and involves several key steps:

1. **Centromere Recognition and Nucleation:**
- The initial step involves recognition of the centromere by specific DNA-binding proteins, such as CENP-A, a histone variant enriched at centromeres.
- These proteins recruit other factors, including CENP-C, which acts as a scaffold for further kinetochore assembly.
2. **Inner Kinetochore Formation:**
- The inner kinetochore, the region directly adjacent to the centromeric DNA, is composed of a network of proteins, including CENP-A, CENP-C, CENP-N, and CENP-T/W/S/X.
- These proteins form a platform for the assembly of the outer kinetochore.
3. **Outer Kinetochore Assembly:**
- The outer kinetochore, facing the spindle microtubules, comprises a diverse set of proteins, including Ndc80 complex, Knl1/Mis12 complex, and the microtubule-binding protein dynein.
- The Ndc80 complex is critical for microtubule attachment and stability, while the Knl1/Mis12 complex acts as a bridge between the inner and outer kinetochores.
4. **Microtubule Capture and Attachment:**
- Once the outer kinetochore is assembled, it can capture and attach to microtubules emanating from the spindle poles.
- This attachment is dynamic and regulated by the interplay of microtubule-binding proteins, motor proteins, and regulatory signals.
5. **Kinetochore-Microtubule Dynamics and Error Correction:**
- After initial attachment, the kinetochore-microtubule interaction undergoes cycles of attachment, detachment, and reattachment, ensuring proper chromosome alignment.
- Error correction mechanisms are in place to ensure that each chromosome is attached to microtubules from both spindle poles, preventing chromosome missegregation.

The regulation of kinetochore assembly involves multiple signaling pathways, including the Aurora B kinase pathway, the SAC (spindle assembly checkpoint) pathway, and the PP2A phosphatase pathway. These pathways ensure proper kinetochore assembly, chromosome alignment, and timely progression through mitosis.'
```"

Proteins (1)

Compounds (1)