Article on a protein and its mechanism which is responsible for the proper alignment of chromosomes during cell division. Written for an assignment.

Based on: NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force

Recently, scientists have discovered the mechanism and proteins responsible for the accurate positioning of chromosomes in a cell’s spindle during metaphase.

A cell’s spindle during metaphase is like two rafts on water, connected to each other by ropes on either sides. The rafts float further apart from each other as the ropes stretch and elongate. A fisherman sits on each raft, facing the other. Their fishing lines hook onto the same fish, which they wrestle back and forth towards the middle.Similarly in a spindle, kinetochore microtubules (“fishing line”) latch onto either sides of the chromosome (“fish”), while the interpolar microtubules (iMTs; “rope”) expand. The chromosomes are pushed and pulled until they line up at the spindle middle. This oscillating movement is regulated by the Nucleolar and Spindle-Associated Protein (NuSAP).

While the idea of NuSAP being a regulator of chromosome oscillation is not new, how exactly it accomplishes that has not been established until recently. Researchers from the National University of Singapore, through the use of 3-Dimensional imaging, found that NuSAP achieves this through association with another protein, Kinesin-like DNA-binding protein (Kid).

Kid is a motor protein that can attach to a chromosome on one end, and iMT on another. Early phases of the research revealed that high amounts of NuSAP cause chromosomes to be misoriented and misaligned from the center. Thus, Kid, which can adhere to and steer chromosomes, was suspected to be involved.

It was later discovered that NuSAP directly interacts with Kid. Their interactivity immensely improves the speed in which Kid glides across the iMT, while connected to and pulling the arm of the chromosome, similar to how clothes pegged onto a laundry line can still be dragged along the line just by pulling the peg.

The relationship between NuSAP, Kid and chromosome oscillation was further proven when the depletion of either NuSAP or Kid led to a tremendous drop in the movement and speed of the oscillating chromosomes. Altogether, these findings cement the consequential roles of NuSAP and Kid with regards to ensuring that chromosomes are perfectly arranged during cell division.

This breakthrough has profound implications for cancer research. Professor Liou Yih-Chenrg, one of the researchers, revealed that they are currently studying the cancer regulation prospects of NuSAP. Earlier studies had shown that cancer increases NuSAP production, which messes up the alignment, separation and number of chromosomes that go into each daughter cell. Ultimately, this study provides a basis to develop a NuSAP-targeting drug to slow down NuSAP production and propagation of cancerous cells.

Reference:

Li, C., Xue, C., Yang, Q., Low, B. C., & Liou, Y. C. (2016). NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force. Nature communications, 7(1), 1-14.