In eukaryotes, cells of the body divide to make more cells in a process called mitosis. Reproductive organ cells undergo another sort of cell division called meiosis. In these processes, cells enter several phases to achieve division. Kinetochores play an important role in cell division, ensuring the proper distribution of DNA to daughter cells.
TL;DR (Too Long; Didn't Read)
Kinetochores and nonkinetochore microtubules are quite different in structure. They both work together to ensure the proper distribution of DNA to daughter cells in cell division.
Why Is Mitosis Necessary?
Eukaryotic cells undergo mitosis for new or growing tissues and for asexual reproduction. One cell divides into two new daughter cells, splitting the nucleus and chromosomes in order to do this. These new cells are identical.
In order for this process to take place successfully, the chromosome number of cells must be maintained, meaning they must be copied for each new daughter cell. Humans have 23 pairs of chromosomes in each cell. Each chromosome stores DNA. The chromosome pairs are named sister chromatids, and the point at which they meet is called the centromere.
Stages of Mitosis
Cell division’s goal is to copy genetic material into new daughter cells in such a way that they are able to function properly. For this to happen, each unit of DNA must be recognized, so there must be a connection between it and other parts of the cell for distribution, and there must be a way to move the DNA to daughter cells.
Between cell divisions, the cell is in a phase called interphase, which consists of the first gap or G1 phase, the S phase and the second gap or G2 phase.
After interphase, mitosis begins with prophase. At this point chromatin in the nucleus is duplicated. The resulting sister chromatids are twisted compactly. The nucleolus goes away, and a structure called a spindle forms in the cytoplasm of the cell, made of spindle fibers.
Prometaphase follows. In this step, there are nuclear envelope fragments in the cytoplasm. The spindle’s microtubules, or long tubelike protein strands, advance upon the chromosomes to begin their work. At the adjoining centromere between the sister chromatids, a protein complex called a kinetochore appears. Microtubules attach to this new structure.
In metaphase, centrosomes form at the opposing cell poles. The chromosomes arrange themselves in a line. Microtubules stretch toward the centrosomes, and a spindle is made. The microtubules perform the anaphase slide, moving the chromosomes until they are centralized on the cell’s equator.
During anaphase, the paired chromatids are separated. These form new chromosomes. Their centrosomes are pushed apart by nonkinetochore microtubules. The chromosomes are moved to the opposite ends of the cell.
Telophase results in cellular elongation by the nonkinetochore microtubules. The former nuclear fragments help to create new nuclei for the daughter cells. Then the twisted chromosomes loosen.
Finally, in cytokinesis, the actual cytoplasm of the cell is split to result in the new daughter cells.
What Is a Kinetochore?
In 1880, anatomist Walther Flemming discovered the attachment site for mitotic spindles on chromosomes. This was the kinetochore. More recently, human kinetochores have been elucidated at a rapid pace.
The kinetochore definition in biology is a protein complex that forms on chromosomes at their centers, in an area called the centromere. Kinetochores play the crucial role for properly distributing DNA to new daughter cells in mitosis.
This protein complex is considered a macromolecule. While the DNA of different organisms varies widely, kinetochores are very similar across species, and are thus conserved.
Differences Between Kinetochores and Nonkinetochore Microtubules
Kinetochores differ from nonkinetochore microtubules in numerous ways. Their structural difference is the first difference. Kinetochores are large structures made of many different proteins, assembled at the centromeres of chromosomes.
Kinetochores serve as a bridge between the DNA of a chromosome and nonkinetochore microtubules. Nonkinetochore microtubules are polymers that work with kinetochores to align and separate chromosomes. Nonkinetochore microtubules can be long and spindly, and they serve different functions. These different structures must work together, however, to achieve control of chromosomes and their movement during mitosis.
The Function of a Kinetochore
Kinetochores essentially work as tiny machines that interact with cellular structures to move chromosomes during cell division. This is a big responsibility for the kinetochore; if not moved properly, errors in the DNA could lead to deleterious genetic disorders or perhaps to cancer. A kinetochore needs a functional centromere so it can assemble on chromosomal DNA and get to work on its crucial role.
The histone centromere protein A, or CENP-A, forms nucleosomes on centromeres. It serves as the site for kinetochores to form. CENP-A nucleosomes work with CENP-C, in the inner kinetochore, and this allows the kinetochore to be assembled so the chromatin to be copied. The kinetochore is used as a stable method of DNA recognition so mitosis can proceed.
Kinetochore and Nonkinetochore Interaction
Once kinetochores are allowed to assemble on a chromosome, proteins gather and begin to build that aforementioned machine. In vertebrates, there can be over 100 proteins in one kinetochore. The inner kinetochore consists of proteins that interact with the chromatin’s centromere. The outer kinetochores’ proteins work to bind nonkinetochore microtubules. This is another difference between kinetochores and nonkinetochores.
The assembly of the kinetochore is carefully conducted through the cell cycle so that once a cell enters mitosis, a dynamic assembly of the kinetochore can happen in minutes. Then the complex can disassemble as needed. The control of kinetochore assembly is assisted by phosphorylation.
Kinetochores must work with many nonkinetochore microtubules directly. The complex called Ndc80 allows this interaction. It is a bit of a dance, as the microtubules are changing in length as they polymerize and depolymerize. The kinetochore must keep up. This “dance” generates force.
During anaphase, the kinetochores get seized by nonkinetochore microtubules from the opposite poles and are pulled by those microtubules so the chromosomes can separate. The microtubule motors such as kinesin and dynein aid this. Additional force is generated when the microtubules depolymerize. The kinetochore acts as a controller of the microtubules’ forces so it can line up chromosomes for segregation.
Checking for Errors
The dynamic kinetochore is not just a tiny machine moving chromosomes apart. It also works as a check on quality control. Any mistakes made in the process could result in genetic errors. Kinetochores also work to stop faulty attachments with microtubules; this is aided by Aurora B kinase via phosphorylation.
Near the core of centromeres, a protein complex called Pcs1/Mde4 works to prevent improper kinetochore attachments.
For anaphase to happen properly, errors must be corrected, or else anaphase needs to be delayed. Proteins help to track down any of these errors; an error results in a signal at the kinetochore that results in the stopping of the cell cycle prior to anaphase.
In sum, kinetochores differ from nonkinetochore microtubules in both structure and function. Both must work together to achieve successful cell division and conservation of DNA in new daughter cells.
A New Frontier
Researchers continue to uncover how the structure and function of kinetochores affect chromosome segregation in mitosis and meiosis. As more research unfolds, scientists will hopefully have a clearer view on how the kinetochore assembly works during DNA replication, among other potentialities. This small but mighty machine keeps cell division running smoothly, and it is worth further study.