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BRCA1 touches up microRNAs

The Journal of Cell Biology
The Rockefeller University Press
Publication Date
DOI: 10.1083/jcb.1972iti2
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JCB_1972iti.indd In This Issue JCB • VOLUME 197 • NUMBER 2 • 2012162 Text by Mitch Leslie [email protected] RNF169 flips the repair switch P oulsen et al. describe an enzyme that helps a cell determine which repair meth- od to use on DNA double-strand breaks (DSBs). Unrepaired DSBs can incite genomic chaos, spurring sections of chromosomes to relocate or even vanish. To ensure that doesn’t hap- pen, a cell wraps a molecular bandage around a DSB. Enzymes arrive at the injury and ubiquitylate the surround- ing chromatin. In turn, the ubiquitin attachments lure DNA repair proteins such as BRCA1 and 53BP1. By analyzing vertebrate genomic sequences, Poulsen et al. identi- fi ed a previously unrecognized ubiquitylating enzyme, RNF169. To their surprise, the researchers discovered that RNF169 has a different function from the other ubiquitylating enzymes, including its close relative RNF168. Although RNF169 homes in on DSBs, it doesn’t ubiquitylate chromatin. Instead, it rebuffs certain repair proteins by competing for binding sites on ubiqui- tylated chromatin. For example, the team found that boosting levels of RNF169 in cells prevented BRCA1 and 53BP1 from gathering at damaged DNA. RNF169’s role, Poulsen et al. suspect, is to favor one DNA repair mechanism. The more accurate method is homolo- gous recombination, in which the damaged chromosome swaps sequences with a sister chromatid. However, only cells that are about to divide and have copied their DNA can perform this type of repair. By contrast, all cells can use the other mechanism, nonhomologous end joining, which involves stitching the broken DNA ends together. 53BP1 and a related repair enzyme inhibit homologous recombination, but the team found that RNF169 encourages cells to use this higher- fi delity method. Poulsen, M., et al. 2012. J. Cell Biol. BRCA1 touches up microRNAs B RCA1, the well-known breast cancer susceptibility gene, helps

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