Figure 4.

DDX11 cellular roles and related phenotypes observed in WABS patients. (A) Formation of chromatin TADs (topologically associating domains) in interphase cells is due to the loop extrusion activity of the cohesin-Scc2 complex. TAD boundaries are defined by the CCCTC-binding factor (CTCF), a sequence specific DNA binding protein that acts as a chromatin insulator [84]. A possible function of DDX11 in promoting cohesin loop extrusion activity has not yet been demonstrated. Nevertheless, a role of DDX11 in chromatin spatial organization at pericentromeric and sub-telomeric regions was proposed [53]. The DNA binding mode of the cohesin-Scc2 complex is only indicative. (B) DDX11 was proposed to recruit the RNA polymerase I complex at the rRNA gene arrays in the nucleolus and to promote rRNA synthesis [12]. DDX11 loss produces shortage of the ribosome pool and a general reduction of the mRNA translation causing the birth defects observed in WABS probands. (C) DDX11 promotes sister chromatid cohesion establishment with the help of Timeless during S phase [9]. Resolution of G-quadruplex structures (especially at the rRNA gene arrays and, possibly, at other difficult-to-replicate templates) assists DNA entrapment by cohesin by a not yet clarified mechanism (see text for details).