Posted by Cassandra Brooks

[Entry posted at 4th February 2010 07:13 PM GMT]

 

Repeat untranscribed DNA sequences are generally thought to be genetic junk at best, harmful at worst, but in ribosomes they are essential to repairing DNA damage, according to a study published this week in Science.

Ribosome functional complex Image: Wikimedia commons

Ribosomal DNA (rDNA) codes for the RNA that makes up a major component of ribosomes, the site of protein synthesis. Ribosomal RNA (rRNA) comprises 80% of the RNA found in a typical cell and is highly conserved from bacteria to humans. Virtually every species has a different number of these untranscribed repeats in their rDNA from only a few in bacteria to thousands in plants and animals. Why these repeat copies were present in the cell was not known, but now researchers at the National Institute of Genetics (NIG) in Mishima, Japan, have shown that these repeat arrays are critical in two processes that facilitate DNA repair.

"For the first time, this study suggests a possible reason for this rather special organization of the rDNA," said Frank Uhlmann, a molecular biologist with Cancer Research UK who was not involved in the study. "And it will surely prompt further investigation."

Research led by Satoru Ide at NIG compared a wildtype yeast strain with 110 repeats to mutant strains with 80, 40 and 20 repeats. They exposed all strains to two mutagens, methyl methanesulfonate (MMS) and ultraviolet radiation (UV), and found that the lower copy strains were much more sensitive to DNA damage.

The difference, they found, had to do with the organization of sister chromatids -- the two identical copies of each chromosome -- in the cells. Sister chromatids need to stay tightly bound to maintain their key role in cell division, but in lower copy strains they were pushed further apart. The lower copy strains were also more vulnerable to damage because a key protein regulating protein assembly, condensin, was impaired.

The authors further found that the low copy strains had higher levels of DNA transcription; conversely, when they blocked transcription, DNA damage remained normal. This led them to speculate that the high transcription rate was the ultimate culprit interfering with sister chromatid cohesion and condensin association, and that the untranscribed repeat regions were serving a protective role.

These findings were particularly interesting, said Luis Aragon, a molecular biologist at the Imperial College London in an email to The Scientist, because they imply that DNA transcription might both impair cohesion in the sister chromatids and lead to DNA damage -- two processes that are generally not viewed to influence each other.

"Ribosomal DNA has the highest transcription level in the cell," said Takehiko Kobayashi, a molecular biologist at the NIG and senior author on the paper. Thus his research team hypothesized that a high number of amplified sequences might have evolved to prevent and repair DNA damage.

"While we suppose the silent copy does nothing to produce ribosomal RNA, they are likely essential for repairing rDNA," he said.

The fact that the number of copies actually determines the yeast's sensitivity to DNA damage may account for the high repeat variability in different species, Kobayashi said. For example, some plant species have more than 30,000 copies of rDNA repeats. "Plants cannot escape from sunlight and thus they are suffering from more DNA damage from UV light," he said. "Maybe these extra copies protect them against this damage."

"It's been a long-standing puzzle why there are so many copies of the ribosomal DNA repeat," Uhlmann said. "Everyone was aware of the unexplained observation." But Kobayahsi and his colleagues provide evidence that evolution actually appears to have selected for these repeat arrays to protect against DNA damage, he added.