A family of macrodomain proteins reverses cellular mono-ADP-ribosylation
Gytis Jankevicius,Markus Hassler,Barbara Golia,Vladimir Rybin,Martin Zacharias,Gyula Timinszky,Andreas G. Ladurner +6 more
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TLDR
These discoveries establish the complete reversibility of PARP-catalyzed cellular ADP-ribosylation as a regulatory modification and identify a family of macrodomain enzymes present in viruses, yeast and animals that reverse cellular ADp-ribsylation by acting on mono-ADP- ribosylated substrates.Abstract:
ADP-ribosylation is a reversible post-translational modification with wide-ranging biological functions in all kingdoms of life. A variety of enzymes use NAD(+) to transfer either single or multiple ADP-ribose (ADPr) moieties onto distinct amino acid substrates, often in response to DNA damage or other stresses. Poly-ADPr-glycohydrolase readily reverses poly-ADP-ribosylation induced by the DNA-damage sensor PARP1 and other enzymes, but it does not remove the most proximal ADPr linked to the target amino acid. Searches for enzymes capable of fully reversing cellular mono-ADP-ribosylation back to the unmodified state have proved elusive, which leaves a gap in the understanding of this modification. Here, we identify a family of macrodomain enzymes present in viruses, yeast and animals that reverse cellular ADP-ribosylation by acting on mono-ADP-ribosylated substrates. Our discoveries establish the complete reversibility of PARP-catalyzed cellular ADP-ribosylation as a regulatory modification.read more
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Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer
Akihiro Fujimoto,Mayuko Furuta,Yasushi Totoki,Tatsuhiko Tsunoda,Mamoru Kato,Yuichi Shiraishi,Hiroko Tanaka,Hiroaki Taniguchi,Yoshiiku Kawakami,Masaki Ueno,Kunihito Gotoh,Shunichi Ariizumi,Christopher P. Wardell,Shinya Hayami,Toru Nakamura,Hiroshi Aikata,Koji Arihiro,Keith A. Boroevich,Tetsuo Abe,Kaoru Nakano,Kazuhiro Maejima,Aya Sasaki-Oku,Ayako Ohsawa,Tetsuo Shibuya,Hiromi Nakamura,Natsuko Hama,Fumie Hosoda,Yasuhito Arai,Shoko Ohashi,Tomoko Urushidate,Genta Nagae,Shogo Yamamoto,Hiroki R. Ueda,Kenji Tatsuno,Hidenori Ojima,Nobuyoshi Hiraoka,Takuji Okusaka,Michiaki Kubo,Shigeru Marubashi,Terumasa Yamada,Satoshi Hirano,Masakazu Yamamoto,Hideki Ohdan,Kazuaki Shimada,Osamu Ishikawa,Hiroki Yamaue,Kazuki Chayama,Satoru Miyano,Hiroyuki Aburatani,Tatsuhiro Shibata,Hidewaki Nakagawa +50 more
TL;DR: In this article, a comprehensive analysis identified point mutations, structural variations (STVs), and virus integrations, in noncoding and coding regions of 300 liver cancers from Japanese individuals.
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PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
TL;DR: New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer.
Journal ArticleDOI
Family-wide analysis of poly(ADP-ribose) polymerase activity
TL;DR: In this article, the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets.
Journal ArticleDOI
Proteome-wide Identification of Poly(ADP-Ribosyl)ation Targets in Different Genotoxic Stress Responses
Stephanie Jungmichel,Florian Rosenthal,Matthias Altmeyer,Jiri Lukas,Michael O. Hottiger,Michael L. Nielsen +5 more
TL;DR: A sensitive proteomics approach based on high-accuracy quantitative mass spectrometry for the identification of PARylated proteins induced under different cellular stress conditions, demonstrating the potential of the approach to uncover hitherto unappreciated processes being controlled by specific genotoxic-stress-induced PARylation.
Family-wide analysis of poly(ADP-ribose) polymerase activity
TL;DR: It is shown that the majority of PARPs generate MAR, not PAR, and it is demonstrated that the H-Y-E motif is not the sole indicator of PARP activity, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets.
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