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TitleMechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch.
Journal, issue, pagesCell Rep, Vol. 33, Issue 12, Page 108529, Year 2020
Publish dateDec 22, 2020
AuthorsLaura C Lehmann / Luka Bacic / Graeme Hewitt / Klaus Brackmann / Anton Sabantsev / Guillaume Gaullier / Sofia Pytharopoulou / Gianluca Degliesposti / Hanneke Okkenhaug / Song Tan / Alessandro Costa / J Mark Skehel / Simon J Boulton / Sebastian Deindl /
PubMed AbstractUpon DNA damage, the ALC1/CHD1L nucleosome remodeling enzyme (remodeler) is activated by binding to poly(ADP-ribose). How activated ALC1 recognizes the nucleosome, as well as how this recognition is ...Upon DNA damage, the ALC1/CHD1L nucleosome remodeling enzyme (remodeler) is activated by binding to poly(ADP-ribose). How activated ALC1 recognizes the nucleosome, as well as how this recognition is coupled to remodeling, is unknown. Here, we show that remodeling by ALC1 requires a wild-type acidic patch on the entry side of the nucleosome. The cryo-electron microscopy structure of a nucleosome-ALC1 linker complex reveals a regulatory linker segment that binds to the acidic patch. Mutations within this interface alter the dynamics of ALC1 recruitment to DNA damage and impede the ATPase and remodeling activities of ALC1. Full activation requires acidic patch-linker segment interactions that tether the remodeler to the nucleosome and couple ATP hydrolysis to nucleosome mobilization. Upon DNA damage, such a requirement may be used to modulate ALC1 activity via changes in the nucleosome acidic patches.
External linksCell Rep / PubMed:33357431 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 3.0 Å
Structure data

11220

6zhx

EMDB-11220, PDB-6zhx:
Cryo-EM structure of the regulatory linker of ALC1 bound to the nucleosome's acidic patch: nucleosome class.
Method: EM (single particle) / Resolution: 2.5 Å

11221

6zhy

EMDB-11221, PDB-6zhy:
Cryo-EM structure of the regulatory linker of ALC1 bound to the nucleosome's acidic patch: hexasome class.
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
  • homo sapiens (human)
KeywordsDNA BINDING PROTEIN / ALC1 / CHD1L / chromatin remodeler / DNA damage response / nucleosome / NUCLEAR PROTEIN / GENE REGULATION / hexasome

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