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Protein involved in childhood disorder linked to cancer

e involved in DNA checkpoint responses. Curious to see if microcephalin is involved in these responses, Stern and Xu, along with Juhie Lee, M.D./Ph.D., engineered cells with reduced microcephalin. They found that when they damaged the DNA in these cells with radiation, the checkpoint response was impaired. They also found that, like other mediator proteins, microcephalin is recruited to sites of DNA breaks. From this, the scientists concluded that microcephalin is an important participant in or regulator of DNA checkpoint responses.

This discovery has many potential therapeutic applications. "The finding that MCPH1 is involved in DNA damage responses suggests that MCPH1 loss of function may promote carcinogenesis," said Stern and Xu. "If so, then restoration of MCPH1 function through gene therapy, or upregulation of pathways involving MCPH1 through other means, could forestall cancer development in individuals known to harbor such mutations. Also, drugs that antagonize MCPH1 in tumors that also have other checkpoint defects may sensitize those tumors to genotoxic therapies."


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Contact: Nicole Kresge
nkresge@asbmb.org
301-634-7415
American Society for Biochemistry and Molecular Biology
31-Aug-2004


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