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How yeast chromosomes avoid the bad breaks
Date:8/7/2011

it's always been very confusing why you would break your genome. It's your blueprint," says Hochwagen. "Obviously, it helps you make new variations and combinations of genes, but it's incredibly dangerous and you really need to make sure that it happens the right way."

In repetitive DNA, this system of breaking and swapping is particularly hazardous, as there are many options that a section of repeat DNA could be swapped with. If the wrong repeat is chosen, a chromosome can gain or lose a large chunk of DNA. In humans, such mistakes have been linked to genetic neurological and developmental disorders, including autism spectrum disorders and schizophrenia.

By studying the highly repetitive DNA that makes up yeast's ribosomal DNA (rDNA), Gerben Vader and Hannah Blitzblau, first authors of the Nature paper and postdoctoral researchers in Hochwagen's lab, have determined that yeast's rDNA is protected from inappropriate recombination by two mechanisms. It was previously shown that heterochromatin prevents chromosome breakage in repetitive DNA. But in their paper, Vader and Blitzblau demonstrate that, ironically, the protective heterochromatin renders the transition zone between the repetitive and non-repetitive DNA particularly fragile. The yeast cell buttresses these borders with Pch2 and Orc1, which prevent chromosome breakage across the entire transition zone. In their absence, rDNA frequently gains or loses repeats.

"We had previously seen very little chromosome breakage in large regions close to repetitive DNA," says Blitzblau. "The finding that the borders of heterochromatin are particularly fragile helps us to understand why the cell invests in specifically protecting these regions."

Although the modes of heterochromatin formation vary between organisms, similar strategies may be at work in higher organisms, too.

"In mice and flies repetitive DNA is also packaged into heterochromatin, and there is evidence that very
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Contact: Nicole Giese
giese@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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