BAF bridges DNA (binding at either end) and nuclear envelope proteins (binding in the middle).

Barrier-to-autointegration factor (BAF) was first described as a cellular activity that prevents retroviral DNA from undergoing suicidal autointegration, but its function in uninfected cells remained obscure. Segura-Totten et al. (page 475) have now performed a detailed biochemical characterization of BAF. The work defines critical functional motifs of this DNA-bridging protein, and suggests that BAF is essential for chromatin decondensation and nuclear envelope assembly and growth.

Previous work had shown that BAF binds to DNA and to proteins containing a LEM domain, a structure that defines a family of nuclear membrane proteins. Using biochemical assays and a panel of site-directed mutants, the authors identified residues of BAF required for the protein to bind to itself, to DNA, and to emerin, a LEM-containing protein. Adding a low concentration of wild-type BAF enhances chromatin decondensation and nuclear growth in a Xenopus egg extract system, but a high concentration of BAF blocks both processes.

The results suggest that LEM-containing proteins bind to the middles of BAF dimers, while DNA binds to the left and right sides. During nuclear assembly, these interactions attach chromatin to the inner nuclear membrane, promoting chromatin decondensation and nuclear envelope growth. The availability of site-directed BAF mutants that produce a range of nuclear assembly phenotypes in the Xenopus system should provide a basis for future studies on BAF function. ▪