Apoptosis Helper Genes Identified

When cells with significant damage to their DNA fail to die, they may become cancerous and proliferate out of control.

"The process of DNA damage-induced cell death is key to both tumor development and the response of cancer cells to therapy,” said Dr. Tyler Jacks of the Massachusetts Institute of Technology (Boston, USA), one of the researchers. "This new work reveals a layer of regulation of this process that is very interesting and very unexpected.”Previous work had shown that the tumor suppressor gene p53 was critical to a cell's ability to respond to DNA damage. A malfunction in p53 could promote formation of certain human cancers. The new study, reported in the April 4, 2002, issue of Nature, discloses that two related genes, p63 and p73, seem to modulate the activity of p53.

"We found that cells and tissues derived from mice lacking both p63 and p73 are unable to undergo apoptosis when challenged with chemotherapeutic agents or radiation,” said Dr. Elsa R. Flores, also on the research team. "Mechanistically, this appears to be due to the fact that some of the genes necessary for cellular suicide that are normally activated by p53 in response to DNA damage are not activated in cells and tissues lacking p63 and p73.”

"We also showed that p53 itself could not be found at the promoters of these apoptotic genes in cells lacking both p63 and p73, and that p63 can be found at these promoters even in the absence of p53. This indicates that p63 and p73 play a previously undetermined role in modulating the activity of p53,” Dr. Flores added.





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