Imagine having to copy an entire book by hand without missing a comma. Our cells face a similar task every time they divide. They must duplicate both their DNA and a subtle pattern of punctuation-like modifications on the DNA known as methylation.
Scientists at Emory University School of Medicine have caught in action one of the tools mammalian cells use to maintain their pattern of methylation. Visualized by X-ray crystallography, the SRA domain of the protein UHRF1 appears to act like a bookmark while enzymes are copying a molecule of DNA.
The team's description of the protein's structure while bound to DNA is published this week in Nature.
Scientists refer to methylation, the addition of a methyl group to DNA, as an "epigenetic" modification because it adds a layer of information on top of the genetic sequence of the DNA itself. It marks genes for silencing, which means they do not manufacture proteins.
"The processes that copy the methylation pattern have to be faithful," says senior author Xiaodong Cheng, PhD, professor of biochemistry and a Georgia Research Alliance eminent scholar. "Otherwise, losing DNA methylation marks can have serious consequences, causing genes to become active at the wrong places and times."
"Gene silencing via DNA methylation is critical for normal development and for curbing the runaway cell division that characterizes cancer," said Peter Preusch, PhD, who oversees biophysics grants at the National Institute of General Medical Sciences of the National Institutes of Health. "Alterations in methylation patterns are also important for generating embryonic stem-like cells from differentiated cells."
In mammalian cells, methylation usually appears on double stranded DNA where the nucleotide Cytosine (C) is followed by Guanine (G). The complementary sequence on the opposite strand is also C then G, and the methylation appears on both Cs.
When a cell is copying its D
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