New Facets in the Regulation of Gene Expression by ADP-Ribosylation and Poly(ADP-ribose) Polymerases

Ryu, Keun Woo; Kim, Dae Seok; Kraus, W. Lee

doi:10.1021/cr5004248

Cited by 122 publications

(112 citation statements)

References 309 publications

(527 reference statements)

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“…Current models postulate that PARP-1 regulates gene expression through two general mechanisms: (1) by modulating chromatin structure (both local and higher order) and (2) by acting as a transcriptional coregulator (with the transcriptional machinery as well as sequencespecific DNA-binding transcription factors) (Kim et al 2004;Krishnakumar et al 2008;Krishnakumar and Kraus 2010b;Ryu et al 2015).…”

Section: Parps In Gene Regulation: a Focus On Parp-1mentioning

confidence: 99%

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

2017

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The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. 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. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field.ADP-ribosylation is a reversible post-translational modification (PTM) of proteins resulting in the covalent attachment of a single ADP-ribose unit [i.e., mono(ADP-ribose) (MAR)] or polymers of ADP-ribose units [i.e., poly(ADP-ribose) (PAR)] on a variety of amino acid residues on target proteins (Gibson and Kraus 2012;Daniels et al. 2015a). This modification is mediated by a diverse group of ADPribosyl transferase (ADPRT) enzymes that use ADP-ribose units derived from β-NAD + to catalyze the ADP-ribosylation reaction. These enzymes include bacterial ADPRTs (e.g., cholera toxin and diphtheria toxin) as well as members of three different protein families in yeast and animals: (1) arginine-specific ecto-enzymes (ARTCs), (2) sirtuins, and (3) PAR polymerases (PARPs) . Surprisingly, a recent study showed that the bacterial toxin DarTG can ADP-ribosylate DNA . How this fits into the broader picture of cellular ADP-ribosylation has yet to be determined.In this review, we focus on the mono(ADP-ribosyl)ation (MARylation) and poly(ADP-ribosyl)ation (PARylation) of glutamate, aspartate, and lysine residues by PARP family members. While many reviews have been written on PARPs in the past decade, we highlight the current trends and ideas in the field, in particular those discoveries that have been published in the past 2-3 years.

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Section: Parps In Gene Regulation: a Focus On Parp-1mentioning

confidence: 99%

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

2017

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“…Moreover, PARP-1 impacts on epigenetic marks by PARylating histones and chromatin remodeling enzymes such as KDM5B, ISWI, ALC1, DNMT-1, CTCF etc. (for review see [26]) or can rearrange nucleosome and linker histone binding through which PARP-1 influences transcription [26]. PARP-1 binds to 90% of the Pol II-transcribed genes and mediates around 3.5% of all transcribed RNAs [26].…”

Section: Epigenetic Alterations and Changes In Gene Expressionmentioning

confidence: 99%

“…(for review see [26]) or can rearrange nucleosome and linker histone binding through which PARP-1 influences transcription [26]. PARP-1 binds to 90% of the Pol II-transcribed genes and mediates around 3.5% of all transcribed RNAs [26]. Besides PARP-1, PARP-2, -7, -10, -14 regulates gene expression [4].…”

Section: Epigenetic Alterations and Changes In Gene Expressionmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

Vida¹,

Abdul‐Rahman²,

Mikó³

et al. 2016

CPPS

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“…[3] ARTD1 is involved in the detection and repair of DNA damage, transcriptional regulation, and modulation of RNA processing. [4] Dysregulation of ARTD1 function is associated with cancer, inflammatory processes, neurodegeneration, and cardiovascular diseases, which makes it an attractive clinical target. [5] Protein PARylation is a tightly regulated process, which, apart from PAR synthesizing enzymes, also involves degrad ing enzymes such as poly(ADP ribose) glycohydrolases (PARGs).…”

Section: Overthelast Decade Biochemical Investigations and In Vivomentioning

confidence: 99%

Real‐Time Cellular Imaging of Protein Poly(ADP‐ribos)ylation

et al. 2016

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Poly(ADP ribos)ylation (PARylation) is an impor tant posttranslational protein modification, and is involved in major cellular processes such as gene regulation and DNA repair. Its dysregulation has been linked to several diseases, including cancer. Despite its importance, methods to observe PARylation dynamics within cells are rare. By following a chemical biology approach, we developed a fluorescent NAD + analogue that proved to be a competitive building block for protein PARylation in vitro and in cells. This allowed us to directly monitor the turnover of PAR in living cells at DNA damage sites after near infrared (NIR) microirradiation. Addi tionally, covalent and noncovalent interactions of selected target proteins with PAR chains were visualized in cells by using FLIM FRET microscopy. Our results open up new opportunities for the study of protein PARylation in real time and in live cells, and will thus contribute to a better under standing of its significance in a cellular context.

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New Facets in the Regulation of Gene Expression by ADP-Ribosylation and Poly(ADP-ribose) Polymerases

Cited by 122 publications

References 309 publications

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

Real‐Time Cellular Imaging of Protein Poly(ADP‐ribos)ylation

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