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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.

SUBMITTER: Corbeski I

PROVIDER: S-EPMC9328677 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Corbeski Ivan I Guo Xiaohu X Eckhardt Bruna V BV Fasci Domenico D Wiegant Wouter W Graewert Melissa A MA Vreeken Kees K Wienk Hans H Svergun Dmitri I DI Heck Albert J R AJR van Attikum Haico H Boelens Rolf R Sixma Titia K TK Mattiroli Francesca F van Ingen Hugo H

Science advances 20220727 30

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<s ...[more]

PMID: 35895815

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