A recent study on the relationship between a specific enzyme and tumor cell growth has attracted medical attention, as researchers from New York University Langone Medical Center found that inhibition of a specific enzyme significantly slowed the growth of some tumor cells associated with genetic mutations in BRCA1 and BRCA2. (BRCA1 and BRCA2 mutations are known to be strongly associated with some breast and ovarian cancers.) If further experiments prove successful, these findings could lead to a new class of targeted therapies against cancers with BRCA1 and BRCA2 mutations, said senior investigator Agnel Sfeir, PhD, a cell biologist at NYU Langone Medical Center. The researchers published their findings in experiments with mice and human cells in the Feb. 2 issue of the journal Nature. Dr. Sfeir and co-workers say they made their findings about the enzyme, called PolQ, in an effort to answer the fundamental biological question of how cells prevent the telomeric ends of linear chromosomes from bonding together. Some cellular DNA repair mechanisms can stitch together telomeres that have broken as part of the cell’s metabolism. But such fusions can impair normal cell growth and survival, the researchers said. In a purely biological sense, our findings demonstrate what we know about the activation of this specific enzyme in several tumors that promotes harmful telomere fusions by inserting entire DNA fragments through a damaging DNA repair signaling pathway called alt-NHEJ,” Dr. Sfeir said. The finding that blocking the action of PolQ reduces cancer cell growth by more than half is quite significant.” In this study, Dr. Sfeir and colleagues at the Scripps Research Institute focused on telomeric DNA, noting that entire fragments of new genetic material are inserted into telomeric DNA when chromosome ends are joined, suggesting that a dozen or more DNA synthesizing polymerases are at work. The researchers then focused on PolQ, in part because it is known to be activated in several tumors, including breast and ovarian cancers, as well as liver and colon cancers. Additional experiments confirmed that PolQ is required for activation of this DNA repair alt-NHEJ signaling pathway. Unlike the major error-free signaling pathway, the HDR signaling pathway, the alt-NHEJ signaling pathway does not use the genetic material of the relevant chromosome as a template to meticulously correct all damaged genetic material. Therefore, alt-NHEJ has a great potential to leave coding errors. Dr. Sfeir added, “Our research will continue to explore the mechanism of action of the alt-NHEJ signaling pathway. and which biological factors, other than PolQ, cells choose between error-prone or error-free DNA repair signaling pathways.”