Protein involved in childhood disorder linked to cancer

A team of scientists has found that a protein involved in a congenital neurological disorder also plays a role in DNA damage repair and thus cancer prevention.

The research appears as the "Paper of the Week" in the August 13 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Primary microcephaly is a rare neurological disorder that results in an abnormally small head due to improper brain formation and growth. Children with this condition may be short, have seizures and have normal or mildly retarded intelligence.

"Microcephalin is the protein encoded by the MCPH1 gene, which, when mutated, is a major cause of microcephaly. We have now identified an important function for microcephalin, which may eventually help explain the connection of MCPH1 with microcephaly, and which links microcephalin function to DNA damage responses that prevent cancer from developing," said David F. Stern, Ph.D., and Xingzhi Xu, M.D./Ph.D. of the Yale University School of Medicine.

Cells incur chronic DNA damage from exposure to normal metabolic byproducts as well as external chemicals and radiation. In order to mitigate this DNA damage, cells must have a mechanism for both detecting damage and for stopping their machinery until the damage is fixed. This feedback mechanism relies on cycle "checkpoint" controls that delay the cell division cycle so that these repair systems have time to work.

"Regulation of these protective processes is coordinated through the action of signaling systems that detect DNA damage, interpret and amplify the signal, and call in appropriate repair and checkpoint responses," said Stern and Xu. "Impairment of checkpoint signaling systems can lead to excessive accumulation of mutations or chromosomal aberrations that are an important aspect of human carcinogenesis."

Microcephalin is very similar in structure to several "mediator" proteins known to b

Contact: Nicole Kresge
American Society for Biochemistry and Molecular Biology

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