Oxygen-Generated Free Radicals Damage Chromosomes

Researchers have found that oxygen metabolism is a major source of the genomic instability observed in NHEJ-deficient cells and, presumably, in all cells. NHEJ, which stands for nonhomologous DNA end joining, is the primary mechanism used by the cell to repair damage to its DNA. Normally, the NHEJ pathway functions to repair any broken DNA, but the NHEJ pathway does not always function at full capacity. In 1999, researchers found that in a cell population where the NHEJ pathway is disabled or missing, about 60% of the cells had at least one chromosome break.

In the March 5, 2002, issue of Current Biology scientists from the University of Southern California (Los Angeles, USA) report that they have been able to identify one of the major causes of damage to cellular DNA. They observed that spontaneous chromosome breaks were partially suppressed by reducing the cellular oxygen tension. Conversely, elevating the level of reactive oxygen species by overexpressing the antioxidant enzyme superoxide dismutase 1 (SOD1) in a transgenic mouse increased chromosome breakage. Damage to chromosomes was more apparent at higher oxygen levels.

According to Dr. Michael Lieber, the oxygen causes its damage through oxidative free radicals—highly reactive atoms with an unpaired electron that can rip through our cells like a bullet.

"Our bodies are being riddled with these bullets every day,” explained Dr. Lieber, "whether we like it or not. And the sorts of double-strand DNA breaks we were looking at are hard to repair. Even if you put the two ends together the best you can, you usually lose a couple of nucleotides along the way. And so every time we get an oxidative free radical hit, which happens several times per day per cell, we lose a little info. Every time it hits your DNA, you wind up with a little less genetic information than you had when you started the day.”
There does not appear to be any easy solution to the problem of oxygen-mediated chromosome damage. As Dr. Lieber says about oxygen, "We need it to survive, but ultimately, it is also probably what kills us.”



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