The Zwilch Kinetochore Protein, also known as ZWILCH, is a crucial component of the kinetochore complex in human cells. It plays a significant role in the proper segregation of chromosomes during cell division, ensuring that each daughter cell receives the correct number of chromosomes. This protein is encoded by the ZWILCH gene and is essential for maintaining genomic stability.
The ZWILCH gene is located on chromosome 15 and encodes a protein that is part of the RZZ (ROD-ZW10-Zwilch) complex . This complex is essential for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores, which are critical for the mitotic checkpoint . The ZWILCH protein itself is composed of several domains that facilitate its interaction with other proteins in the kinetochore complex.
ZWILCH is an essential component of the mitotic checkpoint, a safety mechanism that prevents cells from prematurely exiting mitosis . It ensures that chromosomes are correctly attached to the spindle apparatus before the cell proceeds to anaphase. The protein’s function is closely related to its association with the RZZ complex, which is necessary for the proper localization of other kinetochore proteins .
Mutations or dysregulation of the ZWILCH gene can lead to chromosomal instability, which is a hallmark of many cancers. For instance, defects in the ZWILCH protein have been associated with Buschke-Ollendorff Syndrome, a rare genetic disorder . Research is ongoing to understand the full spectrum of diseases associated with ZWILCH dysfunction.
The study of ZWILCH and its role in the kinetochore complex has significant implications for cancer research and the development of therapeutic strategies. By understanding how ZWILCH functions in normal and diseased cells, scientists can develop targeted therapies to correct or mitigate the effects of its dysfunction.