Fig. 9.

Functional features of ANP32B upon binding of cytochrome c to ANP32B LCAR. (A) Upper — ANP32B LRR (blue oval) binds to the histone dimer H3:H4 (orange and pale orange), whereas the ANP32B LCAR domain (black line) binds to the histone dimer H2A:H2B (magenta and pale pink) [12]. Next, ANP32B incorporates the histone octamer into DNA assembling nucleosomes [12,16]. Lower — ANP32B LRR undergoes changes in its internal dynamics upon binding of Cc to the LCAR. H2A:H2B dimer then competes with Cc for binding to the ANP32B LCAR, thereby releasing Cc from Cc:ANP32B ensembles and facilitating the assembly of nucleosomes. (B) Upper — ANP32B LRR binds to PP2A, whose scaffold subunit is represented in dark grey, the regulatory domain, in light grey; and the catalytic domain, in orange. ANP32B LCAR remains flexible in solution and, eventually, contacts PP2A, thus enhancing the PP2A inhibitory activity of ANP32B_1-251. PP2A inhibition prevents the activation of DNA damage repair mechanisms, as the histone variant γH2AX and RPA remain phosphorylated. Lower — Cc binding to ANP32B LCAR induces long-distance allosteric effects in the ANP32B LRR domain which, in turn, releases ANP32B from the ANP32B:PP2A ensemble. Free PP2A dephosphorylates γH2AX and RPA, a step necessary to repair damaged DNA [8,[35], [36], [37]]. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)