Cancer Development Linked to Faulty Gene Repair Mechanism

Their findings were reported in the January 10, 2003, issue of Science.

An autosomal recessive mutation of the BLM gene causes Bloom syndrome, a rare disorder in which sufferers exhibit an extremely high incidence of cancer in many tissues. In addition to being highly cancer-prone, children born with the syndrome are short throughout their lives, sterile, and have poorly functioning immune systems.

To study the disorder, researchers from the University of North Carolina (Chapel Hill, USA) have worked with a Drosophila model lacking BLM.

Previous research suggested that Drosophila BLM functioned in the repair of DNA double-strand breaks. Most double-strand breaks in flies are repaired by homologous recombination through the synthesis-dependent strand-annealing pathway. The mutant flies no longer have this repair mechanism. In the current study, the investigators found that repair in the mutants was completed by error-prone pathways that created large deletions. This finding suggests that BLM does maintain genomic stability by promoting efficient DNA repair and preventing double-strand break repair by less precise pathways.

"We feel that our results represent a substantial step forward in understanding this important DNA repair gene,” explained senior author Dr. Jeff Sekelsky, assistant professor of biology at the University of North Carolina. "This will aid in our understanding of Bloom syndrome, DNA repair pathways and, perhaps most importantly, cellular defects that lead to cancer.”



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