How Proteins Repair Double-Strand Breaks in DNA

Whenever a cell replicates, DNA suffers about 10 double-strand breaks, which means that both its strands are snapped. These strands spiral against each other to create the famous, double-helix appearance that DNA has. Experts now find out how these accidents are repaired.

The damage is caused by a multitude of factors, including internal ones such as elevated concentrations of free radicals and external ones such as radiation we are exposed to every day. The high rate of damage means that cell multiplication would soon become unfeasible.

The double-strand breaks are very dangerous because they can trigger dangerous gene mutations, of the type that underlie the development of cancer and infertility, among other serious medical conditions.

As such, the only way to accurately multiply a cell is to have a prompt, precise DNA repair mechanism in place. In the new study, conducted by US Department of Energy (DOE) experts, the processes through which these mechanisms operate were surveyed in great detail.

Experts from the Lawrence Berkeley National Laboratory (Berkeley Lab) used cell lines derived from the Drosophila melanogaster fruit fly for the new work. The process they discovered underlying the precise DNA-repair mechanism is both dramatic and entirely new.

Focus was placed on a type of strands called heterochromatin. They are a type of chromatin, the main element making up chromosomes. According to experts, heterochromatin makes up about a third of all chromatin in humans and fruit flies alike.

The repair process happens gradually, in a series of steps, but the succession of these steps is extremely rapid and precise, the Berkeley Lab team explains.

“Heterochromatin poses more of a problem for DNA repair than euchromatin. It has lots of short sequences – many of them only about five base-pairs each – which are repeated millions of times,” explains Berkeley Lab Life Sciences Division expert Gary Karpen

He and his research group were the ones who managed to discover the new repair mechanism.

“Repair of simple repeated sequences is particularly challenging,” adds Berkeley Lab scientist Irene Chiolo. She was the first author of a new study detailing the findings, which is published in the latest issue of the esteemed medical journal Cell.

“In the last 20 years researchers have found that the DNA for each chromosome occupies a separate domain in the nucleus, even when chromosomes are decondensed,” she adds.

“From these ‘chromosomal territories’ the DNA moves to accomplish certain functions, for example gene transcription, by going to where the proteins are. We now observe that similar movements occur even during DNA repair,” the expert concludes.