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DNA editing tool flips its target
Date:9/3/2008

NA, a set of enzymes duplicates the DNA sequence from the parental strand to the new "daughter" strand but not the methylation. Each new daughter strand of the DNA molecule is left with the previously methylated Cs unmethylated. UHRF1 recognizes this "hemi-methylated" DNA and calls in a methyltransferase enzyme to add a second methyl group onto the daughter strand.

"UHRF1 has the important task of making sure the methyltransferase enzyme does its job in the right place and right time," Cheng says.

Mouse cells that have deleted the UHRF1 gene are more sensitive to DNA-damaging agents such as radiation, and mouse embryos without the gene cannot complete development. Other studies have found that cancer cells produce more UHRF1 than non-cancerous cells.

What was an unexpected finding was how the SRA domain of UHRF1 recognizes the hemi-methylated DNA, Cheng says. It flips the methylated nucleotide out of the DNA helix, which only had been seen previously in enzymes that physically modify the DNA.

Cheng says the flipping mechanism could prevent the protein from sliding away once it has found a hemi-methylated site.

"It suggests that it serves as a placeholder, where it recruits other enzymes for faithful DNA methylation or repair enzymes if the DNA has been damaged," he says.


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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

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