New York, May 6 (IANS): A fully functional DNA-copying machinery is essential to stall the growth of cancerous tumours.
A glitch in copying the 46 chromosomes every time a cell divides can leave gaps or breaks, giving rise to chromosomal rearrangements at “fragile sites” that could act as breeding ground for cancer, according to a study.
The “fragile sites” appear in specific areas of the genome where the DNA-copying machinery is slowed or stalled, either by certain sequences of DNA or by structural elements.
"The study is the first to examine thousands of these (fragile) sites across the entire genome and ask what they might have in common," said Thomas Petes, a professor of molecular genetics and microbiology at Duke University School of Medicine in the US.
Each time a human cell divides, it generally makes a copy of its 46 chromosomes to serve as an instruction manual for the new cell.
But from time to time, the information is not copied and collated properly that could give rise to fragile sites that can be a breeding ground for human cancers.
The findings could offer insight into the origins of many of the genetic abnormalities seen in solid tumours.
For the study, researchers carried out comprehensive mapping of the fragile sites in yeast.
The fragile sites are associated with sequences or structures that stalled DNA replication, esoteric entities such as inverted repeats, replication termination signals, and transfer RNA genes, the researchers noted.
“We only published the tip of the iceberg - there is a lot of work you do not see because the connections simply were not significant enough. Even now, we did not find any single sequence motif that would very clearly predict a fragile site," Petes added.
In addition, they found that these fragile sites created a surprisingly unstable genome, resulting in a chaotic milieu of rearrangements, duplications and deletions of pieces of DNA or even the gain or loss of entire chromosomes.
"The ability to analyse these (fragile) sites on a genome-wide basis is an important advance," said Gray Crouse, a professor of biology at Emory University.
The study appeared in the journal Proceedings of the National Academy of Sciences.