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

Ivan Corbeski; Xiaohu Guo; Bruna V Eckhardt; Domenico Fasci; Wouter Wiegant; Melissa A Graewert; Kees Vreeken; Hans Wienk; Dmitri I Svergun; Albert J R Heck; Haico van Attikum; Rolf Boelens; Titia K Sixma; Francesca Mattiroli; Hugo van Ingen

doi:10.1126/sciadv.abo0517

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

Ivan Corbeski, Xiaohu Guo, Bruna V Eckhardt, Domenico Fasci, Wouter Wiegant, Melissa A Graewert, Kees Vreeken, Hans Wienk, Dmitri I Svergun, Albert J R Heck, Haico van Attikum, Rolf Boelens, Titia K Sixma, Francesca Mattiroli, Hugo van Ingen

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

14 Citations (Scopus)

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

Original language	English
Pages (from-to)	eabo0517
Journal	Science advances
Volume	8
Issue number	30
DOIs	https://doi.org/10.1126/sciadv.abo0517
Publication status	Published - 29 Jul 2022

Keywords

DNA/chemistry
DNA Repair
Histone Chaperones/genetics
Histones/metabolism
Molecular Chaperones/genetics
Nucleosomes

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Corbeski, I., Guo, X., Eckhardt, B. V., Fasci, D., Wiegant, W., Graewert, M. A., Vreeken, K., Wienk, H., Svergun, D. I., Heck, A. J. R., van Attikum, H., Boelens, R., Sixma, T. K., Mattiroli, F., & van Ingen, H. (2022). Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF. Science advances, 8(30), eabo0517. https://doi.org/10.1126/sciadv.abo0517

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title = "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 (APLFAD) can assemble the histone octamer in a single step and deposit it on DNA to form nucleosomes. The crystal structure of the APLFAD-histone octamer complex shows that APLFAD tethers the histones in their nucleosomal conformation. Mutations of key aromatic anchor residues in APLFAD 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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doi = "10.1126/sciadv.abo0517",

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T1 - Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF

AU - Corbeski, Ivan

AU - Guo, Xiaohu

AU - Eckhardt, Bruna V

AU - Fasci, Domenico

AU - Wiegant, Wouter

AU - Graewert, Melissa A

AU - Vreeken, Kees

AU - Wienk, Hans

AU - Svergun, Dmitri I

AU - Heck, Albert J R

AU - van Attikum, Haico

AU - Boelens, Rolf

AU - Sixma, Titia K

AU - Mattiroli, Francesca

AU - van Ingen, Hugo

PY - 2022/7/29

Y1 - 2022/7/29

N2 - 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 (APLFAD) can assemble the histone octamer in a single step and deposit it on DNA to form nucleosomes. The crystal structure of the APLFAD-histone octamer complex shows that APLFAD tethers the histones in their nucleosomal conformation. Mutations of key aromatic anchor residues in APLFAD 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.

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

KW - DNA/chemistry

KW - DNA Repair

KW - Histone Chaperones/genetics

KW - Histones/metabolism

KW - Molecular Chaperones/genetics

KW - Nucleosomes

U2 - 10.1126/sciadv.abo0517

DO - 10.1126/sciadv.abo0517

M3 - Article

C2 - 35895815

SN - 2375-2548

VL - 8

SP - eabo0517

JO - Science advances

JF - Science advances

IS - 30

ER -

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

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Keywords

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