Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler.
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.
Gottschalk
Aaron J
AJ
The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Timinszky
Gyula
G
Kong
Stephanie E
SE
Jin
Jingji
J
Cai
Yong
Y
Swanson
Selene K
SK
Washburn
Michael P
MP
Florens
Laurence
L
Ladurner
Andreas G
AG
Conaway
Joan W
JW
Conaway
Ronald C
RC
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
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