Grasping how chromosome copies pull themselves apart
The amount of grip produced by hand-like structures help to divide chromosomes between dividing cells.
When a cell divides, each new cell that forms needs to contain a complete set of DNA, which is stored in structures called chromosomes. So first, the chromosomes duplicate, and the two copies are held together. A protein structure known as a kinetochore then forms on each copy of the chromosome. The kinetochores act as a pair of hands that pull the chromosome copies apart and toward opposite sides of the dividing cell. They do this by grabbing protein ‘ropes’ called microtubules that extend toward the chromosomes from each side of the cell.
Kinetochores grip the microtubule ropes more tightly when the connection is under greater tension. This helps the kinetochores to remain attached to the microtubules that will separate the chromosome copies while releasing the microtubules that would pull both copies to the same side. Previous research has shown that hundreds of finger-like structures made out of a protein group called NDC80 extend from each kinetochore ‘hand’ and attach to the microtubules. What remains a mystery is whether and how the NDC80 fingers grip the microtubules more tightly when tension is greater in cells.
Yoo et al. developed a technique for counting how many of the available NDC80 fingers of a single kinetochore are attached to microtubules within a living human cell. The new technique combines genetic engineering, fluorescence imaging and statistical methods to quantify the attachment of NDC80 to microtubules over time and space.
Yoo et al. found that more NDC80 bound to microtubules when there was greater tension. This relationship between binding and tension depends on an enzyme called Aurora B, which modifies the tip of each NDC80 finger and consequently changes the binding of NDC80 to microtubules. Yoo et al. further showed that Aurora B needs to be properly placed between two kinetochore hands to make NDC80-microtubule binding dependent on tension. Without this tension dependency, chromosomes could segregate unevenly into the newly formed cells — a problem that can lead to cancer, infertility and birth defects. The results presented by Yoo et al. therefore expand our understanding of how these diseases originate and may eventually help researchers to develop new treatments for them.
To find out more
Read the eLife research paper on which this eLife digest is based:
