FANCJ lets chromatin stay true

Schwab et al. show how a protein that unkinks DNA might help cells to maintain chromatin organization during DNA replication.

The DNA replication machinery can run into roadblocks. For instance, a DNA stretch with multiple guanines can develop a kink—known as a G4 quadruplex—that halts copying. The protein FANCJ helps cells overcome these blockages. Faulty FANCJ is one cause of the rare genetic disease Fanconi anemia, which leaves patients prone to leukemia as children, and the gene is often mutated in breast cancers. Researchers have found that FANCJ unwinds G4 quadruplexes in vitro, but they weren’t sure how it promotes DNA replication.

To find out how DNA copying proceeds past obstacles, Schwab et al. monitored individual replication forks. In the presence of a molecule that stabilizes G4 quadruplexes, genome duplication slowed dramatically in cells lacking FANCJ. On the lagging strands of the forks, cells missing FANCJ often showed single-strand gaps where the nucleotides hadn’t been filled in. Although cells with FANCJ can unravel G4 kinks and other blockages, allowing replication complexes to move forward, cells lacking the protein skip over these blockages, leaving unduplicated DNA.

After replicating their DNA, cells normally re-compress the strands to produce the original balance of tightly wound heterochromatin and more relaxed euchromatin. But Schwab et al. discovered that heterochromatin spreads in cells that have lost functional FANCJ. So by enabling DNA duplication to proceed efficiently through obstacles like G4 quadruplexes, FANCJ might help cells regain the correct organization of chromatin domains.