Cancer-promoting protein discovered

TORONTO - Canadian scientists have uncovered a new protein that blocks DNA damage in the cell and thus help spread various cancers, a breakthrough that could pave the way for medical strategies to improve cancer therapies.

The findings by Toronto University researchers - Daniel Durocher, Anne-Claude Gingras and Frank Sicheri - show how cells regulate their genetic material.

Their findings have improved understanding of familial breast and ovarian cancer, as their research shows that the new protein, called OTUB1, inhibits the action of BRCA1, a DNA repair protein that often mutates itself into these cancers, a university statement said Friday.

“In recent years, we have been very good at finding proteins necessary for DNA repair. (But) what we did not appreciate was that gatekeepers existed to inhibit the capacity of the cell to repair DNA. The obvious question now is: Can we enhance the ability of the cell to repair DNA by blocking OTUB1?” the statement quoted lead researcher Daniel Durocher as saying.

The experts used RNA Interference (RNAi) — a system within living cells that helps in controlling which genes are active and how active they are — to uncover the protein OTUB1.

“After exposing cells to radiation, they used RNAi to discover that OTUB1 inhibits a cell’s DNA repair mechanisms, through its role in a process known as ubiquination,” the university statement said.

“Since “mutations in genes that repair our DNA can lead to cancer, infertility and immune deficiency, inhibiting the proteins that block DNA repair could lead to new types of therapeutics for these diseases,” Durocher said.

By inhibiting OTUB1, he said, healthy cells may be better able to withstand cancer treatment with radiation and certain chemotherapy medications such as doxorubicin.

Inhibiting OTUB1 may lead to treatments for other genetic immunodeficiency disorders in which cells lose their ability to repair DNA damage, he added. The findings have been reported in the Aug 19 issue of the journal Nature.