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ALC1: A Chromatin Remodeling Enzyme Activated by Poly(ADP‐Ribose) Polymerase (PARP) and NAD
Author(s) -
Gottschalk Aaron J.,
Swanson Selene K.,
Washburn Michael P.,
Florens Laurence,
Conaway Joan W.,
Conaway Ronald C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.488.2
Subject(s) - chromatin remodeling , chromatin , parp1 , chromatin structure remodeling (rsc) complex , poly adp ribose polymerase , nad+ kinase , histone , biology , microbiology and biotechnology , histone modifying enzymes , biochemistry , polymerase , chemistry , enzyme , dna
ALC1 (Amplified in Liver Cancer 1) is a member of the SNF2 ATPase superfamily and is an oncogene implicated in the pathogenesis of hepatocellular carcinoma. Mass spec analyses suggest that unlike many SNF2 superfamily members, ALC1 does not reside in a multi‐subunit complex, but instead interacts transiently with proteins, including high‐mobility group proteins, histones, PARP1 and PARP2, that are known to be involved in chromatin biology. ALC1 contains a carboxy‐terminal macrodomain that is necessary and sufficient for binding to poly(ADP‐ribose). Free ALC1 has little or no ATPase or chromatin remodeling activity in vitro; however, these activities are strongly activated by PARP1 and the PARP1 substrate NAD. ATPase and chromatin remodeling activities require an intact macrodomain capable of binding poly(ADP‐ribose). ALC1 binds nucleosomes with substantially greater affinity in the presence of PARP1 and NAD, suggesting the poly(ADP‐ribosyl)ation of PARP1 and/or histones may serve as a novel method of targeted chromatin remodeling.