Mitosis under control: new details
Every day, a huge number of cells in our body are divided in two with the formation of two of their exact copies. The loss of control over the cellular mechanisms underlying such division (mitosis) is one of the main causes of the development of malignant tumors.
Very little is known about the cellular mechanisms that control the mitosis process, but scientists at the Technion-Israel Institute of Technology, working under the guidance of Dr. Tim J. Yen, managed to discover a previously unknown biochemical pathway called "mitotic checkpoint factor 2" (mitotic checkpoint factor 2, MCF2). Apparently, this mechanism is crucial in preventing the division of cells that for some reason are unable to properly divide their chromosomes.
The proteins that make MCF2 work have yet to be identified, but the discovery sheds light on one of the fundamental questions of biology and may increase the effectiveness of anticancer drugs that disrupt DNA replication (such as gemcitabine) and prevent mitosis (such as paclitaxel).
At any given moment, about 250 million cells in the body are in the process of mitosis, which is necessary to replace cells that die as a result of normal vital activity. The mitosis control mechanism is a complex set of quality control systems similar to those used on industrial assembly lines, and ensures that a strictly defined and identical set of chromosomes enters each cell.
Tumor cells avoid such quality control, which allows them to shuffle chromosomes and acquire properties that ensure their resistance to treatment and the ability to divide uncontrollably.
MCF2 prevents mitosis by blocking the ubiquitin ligase enzyme known as the anaphase–promoting complex (cyclosome) - anaphase-promoting complex/cyclosome, APC/C. (Anaphase is the fourth of the five phases of the mitotic cell division process, which usually lasts only a few minutes.)
The authors claim that MCF2, together with the previously known group of mitotic checkpoint complex (MCC) proteins, prevent the activation of APC/C using the Cdc20 signaling molecule.
One of the first stages of cell division is DNA doubling. Before the cell is split in two, the proteins of the mitotic control mechanism "check" the mechanical connections between microtubules stretching replicated pairs of chromosomes and chromosomes. If everything is fine, they release APC/C, which is a signal to continue dividing. If any malfunctions are detected, the cell collapses before it has time to separate.
Disruption of the mitosis control system can lead to aneuploidy – an increase or decrease in the number of chromosomes in daughter cells. This increases the risk of cancer and the resistance of malignant cells to treatment.
Some anticancer drugs destroy cancer cells by affecting various mechanisms of mitosis. Despite the differences in the mechanisms of action, drugs such as paclitaxel and gemcitabine affect the processes that are "monitored" by control proteins. The authors believe that a more detailed understanding of the mechanisms of mitosis will help to increase the effectiveness of these and other drugs.
At the same time, the detection of MCF2 raises more questions than it provides answers, because so far a lot is unknown about how the components of the mitosis control mechanism interact with each other and how an exceptionally high accuracy of chromosome separation is achieved.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
16.07.2008