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

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^AD) can assemble the histone octamer in a single step and deposit it on DNA to form nucleosomes. The crystal structure of the APLF^AD-histone octamer complex shows that APLF^AD tethers the histones in their nucleosomal conformation. Mutations of key aromatic anchor residues in APLF^AD 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.