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Protein's essential role in repairing damaged cells revealed
Date:1/6/2009

result. Both feature MRN mutations and significantly predispose a person to immunodeficiency and cancer.

What Ferguson and colleagues discovered is that Mre11 not only senses and communicates damage, it also repairs DNA double-strand breaks by acting as a nuclease, an enzyme that modifies and processes the broken DNA ends.

Research details

The researchers generated mouse models to examine the exact role of Mre11 in the MRN complex. They engineered two mouse strains, one in which Mre11 was disabled completely, and one in which only a single amino acid change was made.

What surprised researchers the most was that making that change to a single amino acid in Mre11 caused consequences as severe as when they eliminated the entire MRN complex.

Taking out the amino acid in Mre11 responsible for nuclease activity caused the mice to develop growth defects, chromosomal abnormalities and sensitivity to DNA-damaging agents. Therefore, researchers could say that the nuclease, or repair, activity of Mre11 proves critical for both MRN function and stability of the genetic material of the organism.

"First, Mre11 signals to the cell by activating the kinase, but it also acts in the repair of double-strand breaks via the nuclease functions. Therefore, it prevents the two individual steps that lead to cancer," Ferguson says.

Implications

The work, called "virtuoso cell engineering" in a Cell preview article, holds particular promise for identifying mutations associated with many cancers.

"What's emerging in the literature from large-scale screening studies of human tumors is that Mre11 may be frequently mutated in certain cancers," Ferguson says.

"This may have implications for diagnoses because tumors associated with different mutations may have different prognoses and respond to different therapies," he says. In particular, mutations in Mre11 may predict how sensitive or resistan
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Contact: Nicole Fawcett
nfawcett@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert  

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