Research sheds light on cancer
progression
MUSC investigators made significant progress in understanding the
connection between gene duplication and the checkpoint mechanism that
protects cells from progression towards cancer. The findings were
reported in the Jan. 24 journal “Proceedings of the National Academy of
Sciences of USA” by Deepak Bastia, Ph.D., Donnelley Professor of
Biochemistry, and his colleagues Bidyut K. Mohanty, Ph.D., research
assistant professor, and Narendra K. Bairwa, Ph.D., research associate.
In the research lab
are Drs. Bidyut K. Mohanty, left, and Narendra K. Bairwa.“Cancers are caused by mutations in genes called tumor suppressors that guard against tumor formation by promoting repair of damaged chromosomes,” explained Bastia. “Or, if the damage is too extensive to be successfully repaired, tumor suppressors cause such cells to be killed and eliminated by a process called apoptosis.”
Cancer-causing mutations can be induced not only by chemicals and ionizing radiation, but also are induced during the normal duplication of DNA. When DNA gets damaged, a pathway called checkpoint response delays cell division until the damage has been repaired, thereby preventing the dissemination of damage DNA to progeny cells.
“The simple baker's yeast cell and humans share some of the same or very similar genes that control the checkpoint pathways and therefore, the simple yeast system serves as a convenient model to study the complex but fundamental process of checkpoint control,” explained Bastia.
The research team made major progress in deciphering the connection between checkpoint control and gene duplication using the simple yeast system.
During normal duplication of DNA, the replication forks often encounter a barrier in their path and stall. The stalled fork is especially fragile and susceptible to breakage and such damage, if not prevented or repaired promptly and completely, it can be potentially carcinogenic.
Bastia and his coworkers discovered the mechanism of checkpoint control during normal DNA duplication. They report that checkpoint proteins protect a stalled fork from the action of a disruptive enzyme (called a helicase or sweepase) that would otherwise dismantle the replication apparatus, thereby increasing cancer susceptibility. Because the yeast cells share so many relevant genes in common with humans, the simple system provides a powerful tool to study basic mechanisms that promote cancer avoidance.
Friday, Jan. 27, 2006
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