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Poly(ADP-ribosyl)ation enhances nucleosome dynamics and organizes DNA damage repair components within biomolecular condensates.
Nosella, Michael L; Kim, Tae Hun; Huang, Shuya Kate; Harkness, Robert W; Goncalves, Monica; Pan, Alisia; Tereshchenko, Maria; Vahidi, Siavash; Rubinstein, John L; Lee, Hyun O; Forman-Kay, Julie D; Kay, Lewis E.
Afiliação
  • Nosella ML; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Kim TH; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toront
  • Huang SK; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toront
  • Harkness RW; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toront
  • Goncalves M; Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
  • Pan A; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Tereshchenko M; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Vahidi S; Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
  • Rubinstein JL; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Lee HO; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Forman-Kay JD; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: forman@sickkids.ca.
  • Kay LE; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toront
Mol Cell ; 84(3): 429-446.e17, 2024 Feb 01.
Article em En | MEDLINE | ID: mdl-38215753
ABSTRACT
Nucleosomes, the basic structural units of chromatin, hinder recruitment and activity of various DNA repair proteins, necessitating modifications that enhance DNA accessibility. Poly(ADP-ribosyl)ation (PARylation) of proteins near damage sites is an essential initiation step in several DNA-repair pathways; however, its effects on nucleosome structural dynamics and organization are unclear. Using NMR, cryoelectron microscopy (cryo-EM), and biochemical assays, we show that PARylation enhances motions of the histone H3 tail and DNA, leaving the configuration of the core intact while also stimulating nuclease digestion and ligation of nicked nucleosomal DNA by LIG3. PARylation disrupted interactions between nucleosomes, preventing self-association. Addition of LIG3 and XRCC1 to PARylated nucleosomes generated condensates that selectively partition DNA repair-associated proteins in a PAR- and phosphorylation-dependent manner in vitro. Our results establish that PARylation influences nucleosomes across different length scales, extending from the atom-level motions of histone tails to the mesoscale formation of condensates with selective compositions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nucleossomos / Poli ADP Ribosilação Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nucleossomos / Poli ADP Ribosilação Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá