June 17, 2004
by Elaine Smith
A protein long thought to be involved in repairing DNA that is damaged during normal metabolic processes is linked to tumour suppression, says a new University of Toronto study.
The researchers discovered that reduction or loss of a protein called Mus81 led to the development of lymphomas and other tumours in mice. The research is published in the June 18 edition of Science.
“When it was discovered in 2000, a lot of people speculated that Mus81 was the missing mammalian enzyme essential for the processing of the Holliday Junction, a DNA recombination structure within the cell,” said senior author Razqallah Hakem, a professor in the U of T Department of Medical Biophysics and a researcher at the Ontario Cancer Institute at Princess Margaret Hospital. “This paper demonstrates Mus81’s role in preventing cancer and illustrates that, contrary to popular belief, it isn’t necessary for processing Holliday Junctions.”
Hakem and his fellow researchers identified mammalian Mus81 and then developed mice lacking the protein. They were able to show that these mice were fertile, something that would not be possible if Mus81 performed the function it was originally believed to have.
Researchers now are exploring whether cancer patients have the Mus81 mutation. If the mutation can be tied to human tumour formation, it should allow people who test positive for such a gene mutation to monitor their health more closely, since they would be at high risk of developing cancer.
In addition, a grant from the National Cancer Institute of Canada will allow the researchers to test mice and tumours with Mus81 mutations for their response to a variety of cancer treatment methods.
“We’ll see how the tumours respond and determine the best treatment strategy to use on patients if they carry the Mus81 mutation,” said Hakem. “We’re hoping to activate the proteins and cellular pathways that can efficiently kill tumours carrying Mus81 mutations.”
Dr. Razqallah Hakem, U of T Faculty of Medicine, (416) 946-2398; e-mail: firstname.lastname@example.org
©2004, University of Toronto.
Involvement of Mammalian Mus81 in Genome Integrity and Tumor Suppression
John Peter McPherson, Bénédicte Lemmers, Richard Chahwan, Ashwin Pamidi, Eva Migon, Elzbieta Matysiak-Zablocki, Mary Ellen Moynahan, Jeroen Essers, Katsuhiro Hanada, Anuradha Poonepalli, Otto Sanchez-Sweatman, Rama Khokha, Roland Kanaar, Maria Jasin, M. Prakash Hande, and Razqallah Hakem
Science 18 June 2004; 304: 1822-1826
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