Centromere and the kinectochore function and structure

MITOTIC DIVISION

1. 6/1/2018


CENTROMERE
AND
KINECTOCHORE
THE DIFFERENCE
Lucky Moyengwe
16000314

2. The centromere is a chromosomal locus that ensures delivery of one copy of each chromosome to
each daughter at cell division. Efforts to understand the nature and specification of the centromere
have demonstrated that this central element for ensuring inheritance is itself epigenetically
determined. The kinetochore, the protein complex assembled at each centromere, serves as the
attachment site for spindle microtubules and the site at which motors generate forces to power
chromosome movement (Manuelidis, 1978). Unattached kinetochores are also the signal
generators for the mitotic checkpoint, which arrests mitosis until all kinetochores have correctly
attached to spindle microtubules, thereby representing the major cell cycle control mechanism
protecting against loss of a chromosome (Karpen, 1997).
Centromere is a region of DNA that is responsible for the movement of the replicated
chromosomes into the two daughter cells during mitosis and meiosis. There is one centromere on
each chromosome, and centromeres are responsible for two major functions (Haaf, 1994).
Centromere, structure in a chromosome that holds together the two chromatids (the daughter
strands of a replicated chromosome). The centromere is the point of attachment of the kinetochore,
a structure to which the microtubules of the mitotic spindle become anchored. The spindle is the
structure that pulls the chromatids to opposite ends of the cell during the cell division processes of
mitosis and meiosis (Manuelidis, 1978). Once separated, each chromatid becomes a chromosome.
Thus, when the cell divides, both daughter cells have complete sets of chromosomes.
One major function of a centromere is joining the sister chromatids. The two copies of a replicated
chromosome are called sister chromatids, and they must stay joined together until it is time for
them to be physically pulled into the two future daughter cells. This ensures that each daughter
cell will get exactly one copy of each chromosome (Haaf, 1994). Cohesins are proteins that keep the
chromatids stuck together. At the beginning of mitosis, the cohesins are distributed evenly along
the chromatids, so they are stuck together along their whole lengths. By metaphase, when all the
chromosomes are lined up at the middle of the cell just before they separate, the cohesins are only
located at the centromere regions, so the sister chromatids are only connected there. In this
diagram, you can see what this looks like (Karpen, 1997).
The other major function of the centromere is attaching the microtubules in the mitotic spindle. In
this function, the centromere directs the formation of the kinetochore, which is a special protein
structure that attaches to the microtubules in the mitotic spindle (Manuelidis, 1978). On each
chromatid, the kinetochore forms at the centromere region of the DNA. Once all of the chromatids
are attached to the mitotic spindle, the microtubules pull the sister chromatids apart into the two
future daughter cells (Karpen, 1997). It’s so important that each chromosome has exactly one
centromere. If a chromosome had two centromeres, it could be broken apart by being pulled in two
different directions during mitosis. If it had no centromeres, it would assort randomly into the
daughter cells and would eventually be lost.
Faithful chromosome segregation also depends on kinetochores, which are specialized
macromolecular structures built upon centromeric chromatin. The dynamic kinetochore structures
connect chromosomes with spindle microtubules, power chromosome movement, and signal the
activation and silencing of the spindle assembly checkpoint (SAC) (Haaf, 1994).

3. Molecular. A human kinetochore contains approximately 200 proteins, many of which are
evolutionarily conserved in other organisms (Karpen, 1997). A histone H3 variant, CENP‐A and
associated constitutive centromere proteins lay the foundation for kinetochore build‐up. Multiple
kinetochore‐localised microtubule‐binding proteins including the Ndc80 complex help regulate
chromosome movement. The SAC signalling originates from kinetochores and contributes to the
fidelity of chromosome segregate (Manuelidis, 1978).
The eukaryotic kinetochore is a multi-protein machine that segregates chromosomes during cell
division. To ensure accurate chromosome segregation, it performs three major functions using
disparate molecular mechanisms. It operates a mechanosensitive signaling cascade known as the
spindle assembly checkpoint (SAC) to detect and signal the lack of attachment to spindle
microtubules, and delay anaphase onset in response (Karpen, 1997). In addition, after attaching to
spindle microtubules, the kinetochore generates the force necessary to move chromosomes.
Finally, if the two sister kinetochores on a chromosome are both attached to microtubules
emanating from the same spindle pole, they activate another mechanosensitive mechanism to
correct the monopolar attachments. All three of these functions maintain genome stability during
cell division (Haaf, 1994)

4. REFERENCES
Haaf T, Ward DC. 1994. Structural analysis of alpha-satellite DNA and centromere proteins using
extended chromatin and chromosomes. Hum. Mol. Genet. 3:697–709
Karpen GH, Allshire RC. 1997. The case for epigenetic effects on centromere identity and
function. Trends Genet. 13:489–496
Manuelidis L. 1978. Chromosomal localization of complex and simple repeated human DNAs.
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