Researchers probe checkpoint signaling responses in unprecedented ways

As published in the April 15th issue of Genes and Development, Dr. Karlene Cimprich and colleagues at Stanford University have determined the minimal DNA structure sufficient to activate the ATR-mediated DNA damage checkpoint.

"We are very excited about these results," says Dr. Cimprich. "The ability to precisely define and manipulate the nature of the checkpoint activating structure in an experimental system will enable us to control, quantitative and probe checkpoint signaling responses in unprecedented ways."

Using Xenopus egg extracts as a cell-free system, the researchers found that single-stranded DNA annealed with primers specifically triggers the ATR-mediated checkpoint response. While many proteins involved in the DNA damage response have been uncovered, this type of structural information is quite novel and valuable. The elucidation of the first defined DNA structure capable of eliciting the ATR checkpoint will aid researchers to further identify additional checkpoint proteins, as well as understand how checkpoint signals are generated and regulated inside the cell.

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