Many kinds of cancer are associated with areas where human chromosomes break, and now researchers have found out why these chromosomes break.
The study was conducted by a team of researchers led by Catherine Freudenreich at Tufts University.
As part of the study researchers focused on one particular human common fragile site that is a normal part of chromosome structure, but is prone to breaking.
Earlier researches have predicted the flexibility of the DNA helix in this particular common fragile site by calculating the twist angle between consecutive base pairs and found that there were several points of high flexibility, suggesting that the flexibility was connected to the fragility.
In the current study, researchers used yeast artificial chromosomes to test this idea because it allowed them to look at the region in a more detailed way than looking at human chromosomes and to monitor the replication process.
"It is an area that has a tumour suppressor gene - a gene whose absence can cause tumours. If you delete that gene or delete part of that gene so it doesn't work anymore, that can lead to tumours. The fact that there is fragility in the same region that this gene is located is a bad coincidence. Fragility can cause deletions and deletions can cause cancer, so you want to understand the fragility because that might be what's causing cancer," Freudenreich said.
The study found that these regions of predicted high flexibility, plus a region near a cancer cell breakpoint and a control region caused breakage of a yeast chromosome.
The researchers hypothesized that the chromosomes broke because replication was stalled in this areas. As cells divide, the DNA inside the cells must duplicate, which is called replication.
"We found that the fragile sequence actually stops replication. So when replication gets there, it has trouble, it stops, it pauses, it can't go further very easily," Freudenreich said.
Most of the time, chromosomes break and heal correctly. The problem arises when they do not heal correctly and instead are deleted or rearranged.
"Cancer cells almost always have some sort of deletions or rearrangements. Something is wrong with their chromosomes that then messes up the genes that are in those areas." She added.
The findings of the study were published in the August issue of journal Molecular Cell.