YALE (US)—The molecular caps at the ends of chromosomes that protect humans against cancer and premature cellular aging show a surprising inability to protect themselves against ultraviolet radiation, according to a new study.
Telomeres—the repeat sequences of DNA at the end of chromosomes that act like plastic tips at the end of a shoelace—are much more likely to be damaged by UV radiation than are other common cellular structures.
“This damage is not repaired. It is as if the cell has decided to defer maintenance to the telomeres,” says Douglas Brash, professor of therapeutic radiology, genetics, and dermatology at Yale University and senior author of the study.
As cells divide over a lifetime, telomeres tend to wear down, and the resulting instability of chromosomes can lead to problems such as increased risk of cancer. As telomeres shorten, cells begin to age, deteriorate and eventually die.
Given their importance, scientists expected telomeres to possess robust defense mechanisms.
Brash and Yale postdoctoral researcher Patrick Rochette, now assistant professor at Laval University, Quebec, tested the hypothesis by bombarding human cells with ultraviolet radiation.
They found 10 times more DNA damage in telomeres than to the p53 gene, to a gene encoding a subunit of the cell’s ribosome or to mitochondrial DNA. And the damage to the telomeres was not repaired. Details of the research were published online April 29 in the journal PLoS Genetics.
“There may be many reasons for this, but it looks like the medicine might be worse than the disease,” Brash says.
An overly robust response to fix damage at the tips of the chromosome might trigger even bigger problems for the cell—such as causing breaks within double strands of DNA, Brash speculates.
The strategy, however, is not without risk. Over many years, the accumulating damage may make the telomeres harder to copy when the cell divides, eventually leading to cell aging and death.
The National Cancer Institute of the National Institutes of Health funded the work.
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