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; Svergun, Dmitri I; Heck, Albert J R; van Attikum, Haico; Boelens, Rolf; Sixma, Titia K; Mattiroli, Francesca; van Ingen, Hugo
(2022) Science advances, volume 8, issue 30
(Article)
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
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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.
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Keywords: DNA/chemistry, DNA Repair, Histone Chaperones/genetics, Histones/metabolism, Molecular Chaperones/genetics, Nucleosomes
ISSN: 2375-2548
Publisher: American Association for the Advancement of Science
Note: Funding Information: This work was funded by Marie Curie Initial Training Network Innovative Doctoral Programme ManiFold grant 317371 EC-FP7/2007-201 to the Utrecht University Bijvoet Centre; Netherlands Organization for Scientific Research grant 723.013.010 (to H.v.I.); European Research Council grant 851564 (to F.M.); Netherlands Organization for Scientific Research grant 175.107.301.10 (to R.B.); Netherlands Organization for Scientific Research grant 700.53.103 (to R.B.); Netherlands Organization for Scientific Research National Roadmap grant 184.032.207 to uNMR-NL, the National Roadmap Large-Scale NMR Facility of the Netherlands; European Research Council grant 731005 to INSTRUCT, for Instruct-ULTRA, an EU H2020 project to further develop the services of Instruct-ERIC; European Research Council project 823839 to Epic-X, an EU Horizon 2020 program INFRAIA project; and European Research Council grant 653706 to INEXT and grant 871037 to iNEXT-Discovery, an EU Horizon 2020 program, which provided financial support for SAXS measurements at beamline P12 operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany). Publisher Copyright: Copyright © 2022 The Authors.
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