Cancer cells are resourceful survivors with plenty of tricks for staying alive. Researchers have uncovered one of these stratagems, showing how cells lacking the tumor suppressor BRCA1 can resume one form of DNA repair, sparing themselves from stagnation or death. The study appears in the January 21st issue of The Journal of Cell Biology.
The BRCA1 protein helps to mend double-strand DNA breaks by promoting homologous recombination. Without it, cells can amass broken, jumbled, and fused chromosomes, which may cause them to stop growing or die. Although cells lacking BRCA1 seem like they should be vulnerable, loss of the protein instead seems to boost abnormal growth.
Recent studies have shown that cells lacking BRCA1 compensate by cutting back on 53BP1. This protein helps orchestrate a different DNA repair mechanism, nonhomologous end joining (NHEJ), and it thwarts a key step in homologous recombination. Researchers think that, in cells without BRCA1, 53BP1 spurs excessive NHEJ that can cause fatal chromosomal chaos. But with 53BP1 out of the way, the cells are able to resume homologous recombination. That might explain why cells that lack BRCA1 and eliminate 53BP1 can withstand traditional chemotherapy compounds and PARP inhibitors, a new generation of anti-cancer drugs that are in clinical trials. But how do cancer cells turn down 53BP1?
Researchers previously found that certain mutant fibroblasts increase production of cathepsin L, a protease that destroys 53BP1. BRCA1-deficient cancer cells take advantage of the same mechanism, according to a team of researchers led by Susana Gonzalo from the Washington University School of Medicine. When they cultured breast cancer cells that were missing BRCA1, the cells stopped growing. After two weeks of lethargy, however, some cells, which the researchers dubbed BOGA cells (BRCA1-deficient cells that overcome growth arrest), began to divide
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| Contact: Rita Sullivan King news@rupress.org 212-327-8603 Rockefeller University Press Source:Eurekalert |
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