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Researchers discover novel function of gene often associated with cancer


In an unusual disease known as Bloom syndrome, patients exhibit an extremely high incidence of cancers in many tissues. In fact, some experts consider Bloom syndrome to be among the most cancer-prone hereditary diseases known.

Although the illness is rare, it fascinates scientists since it can teach them more about how cancers arise and how the body normally suppresses them. Information gleaned from studies of the syndrome should provide insights into other forms of cancer, they say.

Now, working with fruit flies on the gene which, when mutated, causes Bloom syndrome in humans, scientists at the University of North Carolina at Chapel Hill have discovered more about the key mechanisms by which DNA inside cells is repaired.

A report on the findings appears in the Jan. 10 issue of the journal Science. Authors are Drs. Melissa D. Adams and Mitch McVey, both postdoctoral fellows in biology, and Dr. Jeff J. Sekelsky, assistant professor of biology and a faculty member with the UNC Program in Molecular Biology and Biotechnology. McVey is a participant in UNC’s SPIRE (Seeding Postdoctoral Innovators in Research and Education) Program.

Their new paper concerns the BLM gene, Sekelsky said. Inherited imperfections in that gene, also known as mutations, lead to the high likelihood of cancer.

A key feature of the BLM gene identified in 1995 was that it encodes an enzyme that unwinds DNA double helices, he said. BLM is a member of a family of related enzymes. Defects in other members of this family can cause distinct hereditary diseases, including Werner syndrome, in which patients experience accelerated aging. Although BLM is thought to be important in DNA repair, the precise function of the gene has remained unclear.

"In our study, we sought to determine the role of BLM in DNA repair," Sekelsky said. "We conducted our experiments in Drosophila melanogaster, the fruit fly, due to the ease of manipulating the animals genetically.

"We found that the Drosophila BLM gene has a specific function of repairing DNA breaks, such as those that occur after exposure to X-rays."

Adams, McVey and he also discovered that the aberrant DNA repair that occurs in the absence of BLM results in chromosome rearrangements similar to those seen in follicular lymphoma, the most common type of human lymphoma.

"We feel that our results represent a substantial step forward in understanding this important DNA repair gene," Sekelsky said. "This will aid in our understanding of Bloom syndrome, DNA repair pathways and, perhaps most importantly, cellular defects that lead to cancer."

The team is conducting follow-up studies to better understand those important biological processes, he said.

A grant from the Ellison Medical Foundation supported the work.

Bloom syndrome is an autosomal, recessive disorder, meaning that when both parents carry the defective BLM gene, each of their children carries a 50 percent chance of being a carrier of the defective gene, a 25 percent chance of being born with the illness and a 25 percent chance of being entirely free of it.

Besides being highly cancer-prone, children born with the syndrome are short throughout their lives, sterile and have poorly functioning immune systems.

UNC News Services

Note: Sekelsky, Adams and McVey can be reached at 919-843-9400 or 843-9401.

David Williamson | EurekAlert!
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