title: Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler.
abstract: Posttranslational modifications play a key role in recruiting chromatin remodeling and modifying enzymes to specific regions of chromosomes to modulate chromatin structure. Alc1 (amplified in liver cancer 1), a member of the SNF2 ATPase superfamily with a carboxy-terminal macrodomain, is encoded by an oncogene implicated in the pathogenesis of hepatocellular carcinoma. Here we show that Alc1 interacts transiently with chromatin-associated proteins, including histones and the poly(ADP-ribose) polymerase Parp1. Alc1 ATPase and chromatin remodeling activities are strongly activated by Parp1 and its substrate NAD and require an intact macrodomain capable of binding poly(ADP-ribose). Alc1 is rapidly recruited to nucleosomes in vitro and to chromatin in cells when Parp1 catalyzes PAR synthesis. We propose that poly(ADP-ribosyl)ation of chromatin-associated Parp1 serves as a mechanism for targeting a SNF2 family remodeler to chromatin.
authors: The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors: Aaron J
authors: AJ
authors: Gottschalk
authors: Gyula
authors: G
authors: Timinszky
authors: Stephanie E
authors: SE
authors: Kong
authors: Jingji
authors: J
authors: Jin
authors: Yong
authors: Y
authors: Cai
authors: Selene K
authors: SK
authors: Swanson
authors: Michael P
authors: MP
authors: Washburn
authors: Laurence
authors: L
authors: Florens
authors: Andreas G
authors: AG
authors: Ladurner
authors: Joan W
authors: JW
authors: Conaway
authors: Ronald C
authors: RC
authors: Conaway
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000737:chemistry / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D009707:Nucleosomes; C499336:SMARCA1 protein, human; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D011065:Poly(ADP-ribose) Polymerases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C543585:CHD1L protein, human