PB1, also known as BAF180, is a unique subunit of the Polybromo (PBAF) complex. Localisation of PBAF at the kinetochores of mitotic chromosome is consistent with its requirement for cell cycle progression through mitosis (Thompson, 2008). PB1 resembles closely an analogues complex described in yeast containing the subunits Rsc1, Rsc2 and Rsc3 (Xue et al., 2000). Polybromo is composed of 6 Bromodomains, which bind acetylated histones, followed by 2 BAH domains known to act as protein-interaction modules and a C-terminal HMG box. HMGs have been shown to bind nucleosomal DNA. PB1 is widely expressed and thought to target PBAF to chromatin sites, recruit specific effector proteins and alter histone - DNA interactions (Xue et al., 2000), (Thompson, 2008).
The phenotype of PB1 knockout models points to an essential role of this protein in cardiac development. Mouse PB1-/- embryos die during development and show hypoplasia of cardiac ventricular free walls and ventricular septal defect and fail to fail to develop the plexus of coronary vessels. Mice also develop trophoblast placental defects (Wang et al., 2004) (Huang et al., 2008). Truncating mutations of PB1 have been identified in breast cancer suggesting a tumor suppressor role. Although the precise mechanism for its tumor repressor activity is not known yet it is thought that this occurs at least in part, through its ability to regulate p21 (Xia et al., 2008). Here we report the structure of the second and fifth Bromodomain of PB1 at 1.78 Å and 1.63 Å resolution, respectively.
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