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 be 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.”

Media Contact

Nicole Kresge EurekAlert!

More Information:

http://www.asbmb.org

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Pancreatic cancer’s cellular amnesia

Things aren’t always as they seem. Take pancreatic cancer, for example. In up to one in 10 cases, researchers have documented a peculiar characteristic. Some of the pancreatic cells appear…

Innovative Polymer Wound Dressings for Painless and Residue-Free Removal

A new approach enables dressings that adhere firmly to the skin at body temperature, but can be removed easily and painlessly in combination with a cold pack. The dressing adheres…

SETI Institute launches groundbreaking technosignature science and technology

Application deadline for grants is July 15, 2024. The SETI Institute is announcing the launch of a pioneering grants program dedicated to advancing technosignature science. This first-of-its-kind initiative aims to…

Partners & Sponsors