Broken break repair

James King-Holmes / Photo Researchers, Inc

The paper:
P. Ahnesorg et al., "XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining," Cell, 124:301-13, 2006. (Cited in 76 papers)

The finding:
When Stephen Jackson at Cambridge University read a 2003 PNAS paper describing a patient's defective DNA repair that didn't involve any known repair proteins, he wondered what was going on. "So we said, let's go fishing," says Jackson. They pulled out a new protein, similar in sequence to the DNA repair protein XRCC4. Jackson's team found that the gene's mutation in a cell line derived from the patient was contributing to the cells' radiosensitivity, often linked to problematic DNA repair.

The structure:
Jackson, a member of The Scientist's editorial board, named the protein XRCC4-like factor (XLF). Last year he and his colleagues published the crystal structure of XLF, which "shows it is indeed XRCC4-like in its structure." (EMBO J, e-pub ahead of print, Nov. 29, 2007)

Other roles:
Jean-Pierre de Villartay at INSERM in Paris and his colleagues also identified XLF (also called Cernunnos) in the same issue of Cell. They found the gene by examining mutations in patients with immunodeficiency and microcephaly. De Villartay is now developing a knockout mouse to examine Cernunnos/XLF's role in the central nervous system.

The next step:
In this Hot Paper Jackson's team showed that XLF is required for proper repair of DNA double-strand breaks. With the identification of XLF, the entire DNA repair machine is now known, says Jackson. "How is it all controlled, switched on, and switched off? That's a major challenge."