Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome

Zhang, Yajie; Wang, Jianqi; Ding, Ming; Yu, Yonghao

doi:10.1038/nmeth.2603

Cited by 293 publications

(418 citation statements)

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“…An efficient PARylation was also detected on the immunopurified Myc-tagged SRA, whereas a reduced PARylation was detected for the Myc-tagged SRA-deleted mutant of UHRF1 (not shown). Together, these results identified the SRA domain as a preferential site of PARylation, in agreement with the recent report by Zhang et al (47), who identified two sitespecific ADP-ribosylated residues within the SRA domain of UHRF1 by boronate affinity chromatography used to isolate ADP-ribosylated peptides. To a lesser extent, the TTD is also PARylated.…”

Section: P]nadsupporting

confidence: 92%

Poly(ADP-ribose) Polymerase 1 (PARP1) Associates with E3 Ubiquitin-Protein Ligase UHRF1 and Modulates UHRF1 Biological Functions

Vos¹,

Ramy²,

Quénet³

et al. 2014

Journal of Biological Chemistry

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Background: PARP1 and UHRF1 participate in heterochromatin dynamics and the maintenance of DNA methylation, raising the question of whether both proteins cooperate in these events. Results: We reveal a physical and functional poly(ADP-ribose)-mediated interaction of PARP1 with UHRF1 that helps to adjust UHRF1-regulated biological activities. Conclusion: PARP1 is a regulator of UHRF1-controlled H4K20me3 accumulation and DNMT1 expression. Significance: PARP1 associates and cooperates with UHRF1 to regulate heterochromatin-associated events.

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Section: P]nadsupporting

confidence: 92%

Poly(ADP-ribose) Polymerase 1 (PARP1) Associates with E3 Ubiquitin-Protein Ligase UHRF1 and Modulates UHRF1 Biological Functions

Vos¹,

Ramy²,

Quénet³

et al. 2014

Journal of Biological Chemistry

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“…The different methods discussed below use different approaches, both enzymatic and chemical, to achieve this. Zhang et al (2013) recently reported a method to enrich for the universe of ADP-ribosylated peptides using boronate affinity chromatography, in which the ADP-ribose unit forms an ester linkage with boronate beads. Subsequently, the bead-bound peptides can be eluted using hydroxylamine (NH 2 OH), which cleaves the ester bond between a protein-proximal ADPribose and the side chain carboxyl group of an aspartic acid or glutamic acid residue (Fig.…”

Section: New Techniques In Parp Proteomics and Msmentioning

confidence: 99%

“…However, the hydroxylamine chemistry is relevant only in the context of aspartic acid and glutamic acid residues; it cannot be used to screen for ADP-ribosylation of other amino acids, such as lysine or arginine, which are also ADP-ribosylated. Using this approach, Zhang et al (2013) identified >1000 ADP-ribosylation sites on 340 proteins, thus generating an extensive list of both known and previously unknown PARP targets. A similar approach using hydroxylamine was also reported by Gagne et al (2015) to determine the sites of automodification on PARP-1, PARP-2, and PARP-3.…”

Section: Chemical Cleavagementioning

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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“…Similarly, the Drosophila homologue of CHD4 (dMi-2) has been shown to be recruited to active heat shock genes in a PARP-dependent manner (21). Proteomic studies have also indicated that CHD4 and other proteins of the CHD family can undergo poly-ADP-ribosylation; however, the biological effects of this modification are still unknown (22,23).Poly(ADP-ribose) molecules are linear or multibranched chains of ADP-ribose. These polymers are synthesized by PARPs using NAD ϩ as a substrate and are attached covalently to proteins as a post-translational modification (for review see Ref.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

The N-terminal Region of Chromodomain Helicase DNA-binding Protein 4 (CHD4) Is Essential for Activity and Contains a High Mobility Group (HMG) Box-like-domain That Can Bind Poly(ADP-ribose)

Silva

Ryan

Galanty

et al. 2016

Journal of Biological Chemistry

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Chromodomain Helicase DNA-binding protein 4 (CHD4) is a chromatin-remodeling enzyme that has been reported to regulate DNA-damage responses through its N-terminal region in a poly(ADP-ribose) polymerase-dependent manner. We have identified and determined the structure of a stable domain (CHD4-N) in this N-terminal region. The-fold consists of a four-␣-helix bundle with structural similarity to the high mobility group box, a domain that is well known as a DNA binding module. We show that the CHD4-N domain binds with higher affinity to poly(ADP-ribose) than to DNA. We also show that the N-terminal region of CHD4, although not CHD4-N alone, is essential for full nucleosome remodeling activity and is important for localizing CHD4 to sites of DNA damage. Overall, these data build on our understanding of how CHD4-NuRD acts to regulate gene expression and participates in the DNA-damage response.The nucleosome remodeling and deacetylase (NuRD) 3 complex is a conserved transcription co-regulatory complex that is found in all complex animals. It is unique in that it contains both nucleosome remodeling and deacetylase activity (1-6); other co-regulator complexes such as Sin3 (7), Rpd3S (8), and PRC2 (9) only carry a single enzymatic activity. The NuRD complex has been shown to have essential roles in both activation and repression of gene transcription and has links to stem cell renewal and differentiation (10), cell cycle control (11), cancer (for review see Ref. 12), and the DNA-damage response, including DNA double strand break (DSB) repair (13). DSBs are highly cytotoxic; if repaired erroneously or left unrepaired, they can lead to cancer, neurodegeneration, and immunodeficiency (14).One of the defining components of the NuRD complex is chromodomain helicase DNA-binding protein 4 (CHD4). CHD4 mediates the chromatin remodeling activity of the NuRD complex via a SNF2-type DNA translocase domain (15), and evidence has accumulated that CHD4 is important for an effective DNA-damage response and for the maintenance of genomic integrity. For example, the expression level of CHD4 has been shown to increase upon UV irradiation (16). CHD4 has been also reported to be a target of the DNA-damage response apical kinases and to be recruited to DSB sites as part of the NuRD complex (20). This recruitment occurs in a poly(ADP-ribose) polymerase (PARP)-dependent manner. It has been shown that a 750-residue N-terminal fragment of CHD4 (residues 1-758) was sufficient for its recruitment and that this region binds poly(ADP-ribose) (PAR) polymers with the same apparent affinity as full-length CHD4 (20), suggesting that the N-terminal portion of CHD4 contains one or more PAR binding motifs. Similarly, the Drosophila homologue of CHD4 (dMi-2) has been shown to be recruited to active heat shock genes in a PARP-dependent manner (21). Proteomic studies have also indicated that CHD4 and other proteins of the CHD family can undergo poly-ADP-ribosylation; however, the biological effects of this modification are still unknown (22,23).Poly(ADP-ri...

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Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome

Cited by 293 publications

References 25 publications

Poly(ADP-ribose) Polymerase 1 (PARP1) Associates with E3 Ubiquitin-Protein Ligase UHRF1 and Modulates UHRF1 Biological Functions

Poly(ADP-ribose) Polymerase 1 (PARP1) Associates with E3 Ubiquitin-Protein Ligase UHRF1 and Modulates UHRF1 Biological Functions

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

The N-terminal Region of Chromodomain Helicase DNA-binding Protein 4 (CHD4) Is Essential for Activity and Contains a High Mobility Group (HMG) Box-like-domain That Can Bind Poly(ADP-ribose)

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