The current scientific description of the human cell cycle needs some revision, according to researchers.
All science students learn how human cell division takes place. They learn that the copying or replication of the genome, the cell’s DNA, takes place during the so-called S-phase in the cell cycle. The new results show that this is not the case—some regions of the genome are copied only after the cell enters the next crucial phase in the cell cycle called mitosis.
“It has radically altered our views and requires that the textbook view of the human cell cycle be revised,” says Professor Ian Hickson, director of the University of Copenhagen’s Centre for Chromosome Stability and an affiliate of the Center for Healthy Aging.
This unusual pathway for copying of the DNA occurs at specific regions of the human genome called fragile sites, and during mitosis, chromosomes in these fragile areas have a tendency to break. The fragile sites are conserved across species and are frequently associated with undesirable genome rearrangements in connection with the development of cancer.
“We now know that these so-called ‘chromosome breaks’ are not actually broken, but instead comprise a region of DNA that is newly synthesized in mitosis. They appear broken because they are far less compacted than the rest of the chromosome,” adds Hickson.
Cancer cells utilize this unusual form of DNA replication because one of the side effects of the genetic changes that cause cancer is so-called “replication stress.”
The scientists weren’t looking for anything specific but fortunately they saw something very unusual when looking at human cancer cells under the microscope. “When we realized what was happening, it took us about three years to determine the mechanism underlying this phenomenon.”
The scientists already know of two proteins that are essential for this unusual pathway for DNA replication, but now aim to define the full “toolbox” of factors that are required. They can then proceed with studies to identify chemical compounds that block the process. This would constitute the first stage in identifying potential new treatments for cancer.
“Although it has not yet been proven, it seems that the growth of many, or indeed most, cancers in humans is dependent on this process. Hence, the development of a reliable, therapeutic drugs strategy would likely have wide applicability in cancer therapy.
“Our aim is to generate results that will lead to the development of new approaches to treatments of various types of cancer,” says Hickson.
The Nordea-fonden supports research at the Center for Healthy Aging. The Danish National Research Foundation also funded the work, which appears in the journal Nature.
Source: University of Copenhagen