Barrier-to-autointegration factor

Barrier-to-autointegration factor (BAF, encoded by BANF1) is a small non-specific DNA-binding protein that plays critical roles in mitotic nuclear reassembly, chromatin organization, DNA damage response, and innate immunity (UniProt: O75531). Through its dual dsDNA-binding domains, BAF promotes DNA cross-bridging and transiently stabilizes chromatin architecture during cell division, while also restricting cytosolic DNA-sensing pathways by outcompeting cGAS for substrate binding (UniProt: O75531).

BAF is involved in multiple cellular stress responses, including interactions with PARP1 during oxidative damage and recognition of exogenous cytosolic dsDNA at endosome rupture (UniProt: O75531). A known disease association is Nestor-Guillermo progeria syndrome (MIM 614008), characterized by premature lipoatrophy and bone loss (UniProt: O75531).

In Alzheimer's disease, BAF is downregulated in post-mortem human brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.125 (Chaparral AD proteomics). This reduction may contribute to altered nuclear organization and impaired DNA-damage responses observed in neurodegeneration, though the modest magnitude suggests context-dependent effects across subcellular compartments.