Daniela Cimini, an associate professor of biological sciences at Virginia Tech, spoke at the biochemistry seminar on April 30th. In an unusual move, she told two stories about the consequences of mis-segregation and aneuploidy that she had encountered instead of discussing just her published research.
Source: Wikipedia
On April 30th, Daniela Cimini, an associate professor of biological sciences at Virginia Tech, was invited to speak at the biochemistry seminar. Rather than discussing her published research, she told two stories about the consequences of mis-segregation and aneuploidy that she had encountered. Mis-segregation involves a faulty separation of chromosomes in cell reproduction or division. Aneuploidy involves an abnormal chromosome number or an incomplete chromosome set.
Aneuploidy is the leading cause of miscarriages and birth defects, typically causing abnormalities within the sex chromosomes. The growing child cannot tolerate these abnormalities as it develops, causing a miscarriage. Other times, especially if the abnormality is on chromosome 13 or 18, the child will be born but die very quickly after birth.
Aneuploidy can happen in mitosis and meiosis, both processes of cell reproduction. Cimini focuses on mitosis. Aneuploidy is observed in 90 percent of solid tumors and 50 percent of hematopoietic cancers.
Rather than more quantitative work, Cimini uses microscopy for many of her studies. The group will use images and microscopic film to observe mitosis creating two daughter cells— specifically monitoring the vertebrate kinetochore, the mitotic spindles, and the number of chromosomes.
Spindle fibers are the long structures that pull the chromosomes apart in mitosis. Additionally, the kinetochore is a protein structure on the chromatid where spindle fibers attach to the chromosome during division.
Cimini first told a story about the concept of a lagging chromosome or an anaphase lag. Typically in mitosis, a mitotic checkpoint in the biochemical signal pathway shows that all the spindle fibers are attached and that the process should stop, most likely involving tension.
Normally the kinetochore should orient correctly to split into two even daughter cells. However, a mono-orientation can happen, when one kinetochore—but not the other—is attached to the spindle fiber, or when the spindle fibers attach to the same chromosome. Both lead to aneuploidy, the incorrect distribution of chromosomes.
Sometimes a delayed movement in this phase can correct this mistake. The chromosome will tardily be pulled toward the correct location, but can get stuck in the middle, becoming the so-called lagging chromosome. If the chromosome fails to reach the daughter cell, it will form its own micronucleus in the cytoplasm and fall out from both cells.
In Cimini’s experiment, they would monitor these micronuclei through mitosis and observe their segregational defects. They indeed saw defective chromosome condensation in micronucleus as well. With this study, they intend to look further into the aspect of kinetochore condensation as a cause for the mis-segregation.
The next study she discussed pertained to cancer cells and chromosomal instability (CIN), or a high rate of gain and loss of chromosomes. CIN is generally associated with poor cancer patient prognosis. It can be responsible for treatment and drug resistance. The link between aneuploidy and CIN is that disomies in haploid can promote CIN and increase mutation rates.
This is also true in cancer; for example, CIN has been correlated with the degree of aneuploidy in human colorectal cancer cells. However, studying the effect of aneuploidy in cancer cells can be complicated due to the complexity of their karyotypes. Cimini’s approach to this study involved inducing changes in the population background to observe whether that led to CIN.
Aneuploidy promotes chromosomal instability by increasing the rates of chromosome mis-segregation. Furthermore, chromosome mis-segregation can trigger CIN even without aneuploidy. Depending on the specific aneuploidy cell, it can exhibit other specific defects and behaviors. Cimini looks forward to developing her two studies and exploring the consequences of aneuploidy further.