The gene, called PASG (Proliferation Associated SNF2-like Gene), normally works by decreasing the activity of other genes in two different ways: helping to add chemical groups to DNA, in a process known as methylation, or by modifying protein structures called histones that help wind DNA into compact coils.
"In order to grow and stay alive, cells depend on the PASG gene to reduce the activity of other genes, but it's a very complicated process - much like modifying the engine of an F-15 fighter jet while it's flying," says Robert Arceci, M.D., Ph.D., King Fahd Professor and Director of Pediatric Oncology, and director of the study.
The Hopkins team began investigating the PASG gene after finding that its activity is integrally involved in cell growth and mutated forms of the gene occur in acute leukemias. Using genetically engineered mice, Arceci's team knocked out part of the "core engine" of the PASG gene, decreasing methylation throughout the genome and allowing the wrong genes, particularly those associated with premature aging, to be active all the time. The result was that mice with this mutated PASG protein showed signs of premature aging and profound growth problems, including low birth-weight, graying and loss of hair, skeletal abnormalities, reduced fat and early death.
"To keep body tissues working correctly, the PASG gene appears to help cells regenerate, mature and prevent early aging," explains Arceci. "Each cell is programmed with a set number of replications before it dies. With a mutated PASG gene, the cell may replicate only a fraction of the time, and then it dies prematurely," explains Arceci.
"If PASG's methylation ac
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Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
27-Apr-2004