Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF.

Corbeski, Ivan; Guo, Xiaohu; Eckhardt, Bruna V; Fasci, Domenico; Wiegant, Wouter; Graewert, Melissa A; Vreeken, Kees; Wienk, Hans et al. · Sci Adv · 2022

basic_science · Level V

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Abstract

Nucleosome assembly requires the coordinated deposition of histone complexes H3-H4 and H2A-H2B to form a histone octamer on DNA. In the current paradigm, specific histone chaperones guide the deposition of first H3-H4 and then H2A-H2B. Here, we show that the acidic domain of DNA repair factor APLF (APLF<sup>AD</sup>) can assemble the histone octamer in a single step and deposit it on DNA to form nucleosomes. The crystal structure of the APLF<sup>AD</sup>-histone octamer complex shows that APLF<sup>AD</sup> tethers the histones in their nucleosomal conformation. Mutations of key aromatic anchor residues in APLF<sup>AD</sup> affect chaperone activity in vitro and in cells. Together, we propose that chaperoning of the histone octamer is a mechanism for histone chaperone function at sites where chromatin is temporarily disrupted.

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