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

Sci Adv. 2022 Jul 29;8(30):eabo0517. doi: 10.1126/sciadv.abo0517. Epub 2022 Jul 27.

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.

MeSH terms

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

Substances

  • Histone Chaperones
  • Histones
  • Molecular Chaperones
  • Nucleosomes
  • DNA