Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler

Aaron J. Gottschalk, Gyula Timinszky, Stephanie E. Kong, Jingji Jin, Yong Cai, Selene K. Swanson, Michael P. Washburn, Laurence Florens, Andreas G. Ladurner, Joan W. Conaway, Ronald C. Conaway

Research output: Contribution to journalArticlepeer-review

271 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)13770-13774
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number33
DOIs
StatePublished - Aug 18 2009
Externally publishedYes

Keywords

  • Alc1
  • Chromatin remodeling enzyme
  • Macrodomain
  • Poly-(ADP-ribose) polymerase
  • Snf2-like ATPase

ASJC Scopus subject areas

  • General

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