DNA duplication is more likely to have inaccuracies at times of stress that can lead to mutations that may cause disease.
Cells go largely to keep their genomes completely. But when resources are scarce, errors begin to join the DNA code with potential consequences of disastrous, and new research suggests.
At any time the DNA is more vulnerable than when it is copied during a cell division so that it can be split between falling cells. In order to avoid errors in the reconstruction of DNA, cells use proof-reading enzymes that copy the code with high loyalty. Or so it was believed.
A new study led by Grant Brown, a biochemistry teacher at the Donnelly Center for Cellular and Biomolecular Research at the University of Toronto, suggests that the errors of DNA reconstruction at times of stress are much more often than they are worth depressing . Although researchers are studying yeast cells, a similar process could accelerate the rate of propagation in our own cells that lead to cancer and other diseases.
The findings in the magazine were described Molecular Cell.
The discovery came to Brown and David Gallo, a PhD student who did most of the work, surprisingly. They were studying the reproduction of DNA in cells that were raised with a limited supply of nucleotide centers that form letters of the DNA, A, T, C and G. code. "You can think of it as the car Getting out of fuel. We're taking gas from duplicating DNA, "explained Gallo.
Cells may encounter this type of stress when food is short or in a disease, when resources are extinguished by rapidly spreading cancer cells, for example.
To make a copy of their genome, cells decompose the double DNA helix into single strands, where each string acts as a template that a new DNA is synthesized by preparing a complementary base, A with T and C with G. This is usually done by DNA polymerase enzymes rarely "are correct and rarely make mistakes to ensure that lifeprint is transmitted to next generation with high fidelity, "says Brown.
But the lack of DNA building blocks led the cells to call on another type of DNA polymerase, which is more difficult. This was a surprise because it was believed that polymerases that are susceptible to error are related to emergency repair machines that are being implemented in response to physical harm, such as lesions in the DNA caused by UV light or some carcinogenes. And while these enzymes are operating quickly to copy the disadvantaged part of the DNA, they also make mistakes.
The so-called "mutagenic repair" might seem something unusual to protect DNA, but it helps to avoid genome-wrecking situations that aggravate where illegal DNA strands can lead to losing a dose of chromosomes.
"It's better to copy and make some mistakes than to leave untreated and open to chromosomal reorganizations that would exacerbate a great deal for the cell," said Brown.
The study provides strong evidence of the use of polymerases that are susceptible to errors when there is no obvious DNA damage. It suggests that these polymerases may duplicate DNA more than to appreciate and that this could be a greater source of mutations that could lead to disease.
If the same is true for human cells, the perception could have implications for cancer research. Our cells have the same DNA copying machines that predict an error. And rapidly prolonged cancer cells often suffer from what is called a re-duplication stress caused by oncogen, when they run out of fuel because DNA reconstruction rates outweigh supply nucleotide. Under these conditions, the cells could encounter DNA duplication that is susceptible to error, where new mutations could help cancer survive although this continues to be checked by studies in the future.
"The DNA replicas pathway that can be susceptible to mistakes during re-duplication of anogenogen stress can be implemented very well to help cancer cells survive," said Gallo. "This would make it a hot therapeutic target to kill cancer cells selectively."
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