Cutting Away DNA the Mitochondrial Way

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Cutting away DNA the mitochondrial way

When British researchers last year showed that a deletion of DNA within the mitochondria of cells caused a series of related muscle ailments, they revealed a new type of disease-causing genetic defect. Now a team at Emory University in Atlanta suggests it has unraveled the basic mechanism causing the loss of mitochondrial DNA.

"We think we understand how the deletions occur, that the deletions are a direct result of the normal replication process and that the deletion process can occur anytime during [fetal] development," team leader Douglas C. Wallace reported last week at the annual Short Course in Medical and Experimental Mammalian Genetics in Bar Harbor, Maine. "This is a very interesting class of mutation. They are spontaneous mutations; they are not inherited."

Mitochondria serve as power plants inside cells, producing adenosine triphosphate, the key fuel used by cells. A human cell contains 300 to 600 mitochondria, each harboring four to 10 double-stranded circular bits of DNA that hold a few dozen genes. These genes are distinct, and replicate separately, from those packed on the rod-like chromosomes inside the cell nucleus.

Mitochondrial genes reside on two concentric circles of dna called the heavy and light strands. During DNA replication, these strands separate, and each becomes a template upon which a new, identical strand is made. Wallace and his colleagues have identified a series of direct repeats - short segments of DNA with identical sequences of the nucleotides that make up DNA. They propose that during replication of a DNA strand, one repeat can mistakenly join to an identical repeat site further along the strand, creating a loop that breaks off.

"Our model is that during this period when a single-strand region is bowed out, you could have base pairing between this upstream repeat and this downstream repeat to give you [a loop]," Wallace explains. …