18.9: Attachment of Sister Chromatids
As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules. Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall of a microtubule. Such laterally attached kinetochores move along the microtubule wall with the help of the motor proteins and eventually forming a stable head-on attachment with the plus-end of the microtubule. Initially, chromosomes may have a monotelic attachment, where only one sister kinetochore is attached to a single spindle pole, and the other sister kinetochore remains unattached to microtubules. Subsequently, the unattached sister kinetochore connects with the microtubule from the opposite spindle, resulting in an amphitelic attachment. Amphitelic attachment of the sister chromatids is a prerequisite for accurate segregation of the chromosomes.
The kinetochore-microtubule interaction can also result in incorrect attachments. A syntelic attachment is when both kinetochores of the sister chromatids attach to microtubules from the same spindle pole. A merotelic attachment forms when the microtubules from opposite poles bind to the same kinetochore. Syntelic and merotelic attachments result in chromosomal segregation errors and can be corrected by Aurora-B kinase-dependent mechanisms.
Once a single microtubule has established the correct head-on connection with the kinetochore, additional microtubules from the same spindle can bind to the kinetochore, resulting in the formation of a kinetochore fiber. Such kinetochore fibers can contain 10 to 40 microtubules in animal cells.
The correct microtubule-kinetochore binding generates tension within the kinetochore from opposing forces, where the sister-chromatid cohesive force resists the poleward pull along the microtubules. The kinetochore tension triggers an increase in microtubule-binding affinity, thereby locking the stable attachment in place and ensuring the biorientation of sister chromatids.