News ID: 129612
Published: 1152 GMT October 25, 2015

New DNA insights may lead to cancer therapy

New DNA insights may lead to cancer therapy

Researchers at Weill Cornell Medicine have developed a better understanding of a complex mechanism that contributes to the growth of telomeres, the repetitive sequences of DNA that protect the end of a cell's chromosomes.

Each time a normal cell divides, its telomeres shorten, a process that eventually leads to cell death. To avoid this fate, cancer cells maintain their telomere length and continue to divide uncontrollably. The majority of cancer cells use the enzyme telomerase to add DNA to their telomeres. However, about 10 to 15 percent of cancer cells use a different process, or pathway, to maintain their telomere length, said.

This pathway, called ALT, for alternative lengthening of telomeres, exchanges pieces of DNA from one chromosome to another or copies DNA from one portion of a chromosome to another portion. The team discovered vulnerabilities in ALT that investigators could harness for new cancer therapies.

"By understanding what factors, or mechanisms, are required for the ALT pathway to function, we will be able to better develop drugs that block these factors in cancer cells," said senior author Dr. Neal Lue, a professor of microbiology and immunology at Weill Cornell Medicine.

To learn more about the ALT pathway, the researchers used Ustilago maydis, a yeastlike fungus containing telomeres that share many of the same features as human telomeres. By genetically manipulating the fungus, they triggered the ALT pathway, and then showed that eliminating a specific gene prevented the pathway from working. The gene, BLM, encodes an enzyme that separates DNA strands, a process that appears to be important for starting the recombination process, Lue said.

"We knocked out BLM and showed that the ALT pathway is completely dead and that these cells can no longer add DNA to their telomeres," he said. "If we can design an inhibitor against BLM, it would probably be effective in reducing the growth of some cancer cells."


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