Gottschalk Aaron J, Timinszky Gyula, Kong Stephanie E, Jin Jingji, Cai Yong, Swanson Selene K, Washburn Michael P, Florens Laurence, Ladurner Andreas G, Conaway Joan W, Conaway Ronald C
The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13770-4. doi: 10.1073/pnas.0906920106. Epub 2009 Aug 6.
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.
翻译后修饰在招募染色质重塑和修饰酶至染色体特定区域以调节染色质结构方面发挥关键作用。Alc1（肝癌中扩增基因1）是SNF2 ATP酶超家族的成员，具有一个羧基末端大结构域，由一个与肝细胞癌发病机制相关的癌基因编码。在此我们表明，Alc1与包括组蛋白和聚（ADP - 核糖）聚合酶Parp1在内的染色质相关蛋白短暂相互作用。Alc1的ATP酶和染色质重塑活性被Parp1及其底物NAD强烈激活，并且需要一个能够结合聚（ADP - 核糖）的完整大结构域。当Parp1催化PAR合成时，Alc1在体外迅速被招募至核小体，在细胞中则被招募至染色质。我们提出，染色质相关的Parp1的聚（ADP - 核糖基）化作为一种将SNF2家族重塑因子靶向染色质的机制。
