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 +10 more
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It is proposed that poly(ADP-ribosyl)ation of chromatin-associated Parp1 serves as a mechanism for targeting a SNF2 family remodeler to chromatin.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.read more
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The DNA Damage Response: Making It Safe to Play with Knives
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PARP inhibition: PARP1 and beyond
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Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
TL;DR: How the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells is outlined.
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New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs.
Bryan A. Gibson,W. Lee Kraus +1 more
TL;DR: This work has shown that the activity of PARP family members, such as PARP1 and PARP2, is tied to cellular signalling pathways, and through poly(ADP-ribosyl)ation (PARylation) they ultimately promote changes in gene expression, RNA and protein abundance, and the location and activity of proteins that mediate signalling responses.
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Mechanisms of DNA damage, repair, and mutagenesis.
TL;DR: This introductory review will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue.
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