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Tufts researchers discover link between DNA palindromes and disease
Date:7/14/2008

rom a double helix into a hairpin or cruciform like structure in a test tube. It was not known, however, whether these changes can occur inside cells and, if so, affect DNA functioning. In this study, the researchers found that large palindromes stall the replication machinery.

"Replication is carried out by a complex and sophisticated machinery, which has many levels of checks and balances to prevent 'typos' from happening. Long DNA palindromes, however, can occasionally jam this powerful replication machinery," Mirkin explained. The researchers were also able to pinpoint the exact structure causing DNA malfunction. "In all cases it was the formation of the hairpin-like DNA structure in a palindrome that caused the replication to stall," he said.

Other scientists have previously found that when replication slows down, chromosomes break. "Stalled DNA replication could result in the chromosomal breakage during cell division, explaining why DNA palindromes are genomic weak spots."

The study of yeast cells yielded an additional finding. Mirkin and his team found that two proteins within the cell - Tof1 and Mrc1 - enabled replication to proceed through the hairpin-like DNA structures. "These proteins might be key players in protecting the genome from breaking at DNA palindromes," said Mirkin.

Mirkin said he has begun experiments to see if the same results will be observed with human homologues of these proteins.


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Contact: Alex Reid
alexander.reid@tufts.edu
617-627-4173
Tufts University
Source:Eurekalert

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