Nucleosomal Core Histones Mediate Dynamic Regulation of Poly(ADP-ribose) Polymerase 1 Protein Binding to Chromatin and Induction of Its Enzymatic Activity

Pinnola, Aaron D.; Naumova, Natasha; Shah, Meera; Tulin, Adrian

doi:10.1074/jbc.m705989200

Cited by 102 publications

(139 citation statements)

References 43 publications

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“…This suggestion is supported by our previous observation, wherein we demonstrated in vitro that the N-terminal domain of PARP1 suppresses interaction of PARP1 with histones H3 and H4 (19). This might explain the enrichment of PARP Δ300 in active open chromatin observed in vivo in the present work.…”

Section: Zn-finger Domain 1 Is Necessary For the Silencing Of Retrotrsupporting

confidence: 81%

“…2A, arrowheads), suggesting that there is an equilibrium of PARP Δ300 protein binding to chromatin. To investigate the nuclear dynamics of this PARP isoform, we employed the fluorescence recovery after photobleaching (FRAP) approach (19). We compared the FRAP dynamics of PARP Δ300 -EYFP protein with those of full-length previously validated (19,23) PARP1-DsRed in Drosophila polyploid nuclei.…”

Section: Parp C03256mentioning

confidence: 99%

“…To investigate the nuclear dynamics of this PARP isoform, we employed the fluorescence recovery after photobleaching (FRAP) approach (19). We compared the FRAP dynamics of PARP Δ300 -EYFP protein with those of full-length previously validated (19,23) PARP1-DsRed in Drosophila polyploid nuclei. We expressed both recombinant proteins separately in parp C03256 mutant animals using the Armadillo-Gal4 driver, which is expressed ubiquitously (24).…”

Section: Parp C03256mentioning

confidence: 99%

“…For the first approach, we expressed previously verified (6,18,19) UAS::PARP1-DsRed and UAS:: PARP embryonic (PARPe)-EGFP transgenic constructs with G1-Gal4 ubiquitous driver. Ectopic expression of full-length PARP1 protein (PARP1-DsRed) but not the catalytically inactive PARPe protein (PARPe-EGFP) rescues C03256 lethality completely (Table S2).…”

Section: Parp C03256mentioning

confidence: 99%

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Uncoupling of the transactivation and transrepression functions of PARP1 protein

Kotova

Jarnik

Tulin

2010

Proc. Natl. Acad. Sci. U.S.A.

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Poly(ADP ribose) polymerase 1 (PARP1) is a nuclear protein that regulates chromatin remodeling and transcription as well as DNA repair and genome stability pathways. Recent studies have revealed a paradoxical dual role of PARP1 protein in transcription. Specifically, although PARP1 controls transcriptional activation of a subset of genes that are heat shock-or hormone-dependent, it also directly inactivates transcription, establishes heterochromatin domains, and silences retrotransposable elements. However, the domains required for these disparate functions are currently unknown. In this paper, we report the discovery of a previously undescribed mutation in the Drosophila Parp locus. We show that the mutants express a deletion mutant of PARP1 protein with an altered DNA binding domain that carries only the second Znfinger. We demonstrate that this alteration specifically excludes PARP1 protein from heterochromatin and makes PARP1 unable to maintain repression of retrotransposable elements. By characterizing the biological activity of this unique PARP1 mutant protein isoform, we have uncoupled the transactivation and transrepression functions of this protein.chromatin | poly(ADP ribose) polymerase | transcription P oly(ADP ribose) polymerase 1 (PARP1) protein has been known for decades as a nuclear protein that recognizes and binds nicks and ends of DNA and catalyses poly(ADP ribose) (pADPr) synthesis (1). The basic enzymatic reactions catalyzed by PARP1 involve transferring ADPr from nicotinamide-adenine dinucleotide to either a protein acceptor or an existing pADPr chain, the average length of which is 80 or more residues (2). PARP1 protein can modify numerous chromatin proteins in vivo and in vitro (3). A key role of PARP1 was shown in DNA repair and apoptosis (3), where PARP works as a trigger between the DNA repair (4) and apoptotic pathways (5). PARP1 enzymatic activity has also been shown to be required for normal assembly of higher order chromatin structures and for transcriptional activation (6). Moreover, it has been shown that PARP1 regulates the transcription of these genes by inducing chromatin loosening at targeted genetic loci (6, 7). Finally, PARP1 establishes silent chromatin domains and represses retrotransposable elements (8).The characterization of deletion mutants of PARP that distinguish among the varied functions of this protein is essential to establish a more complete understanding of PARP1 protein biology. At present, however, we have identified neither the mechanism of PARP protein targeting to specific chromatin domains nor the mechanism of local PARP activation. Closing these gaps in our current knowledge is complicated because the presence of 18 paralogous PARP proteins (9) in mammals most likely results in corresponding functional redundancies. The Drosophila genome (8, 10, 11) encodes only a single nuclear PARP (PARP1), making this animal an invaluable model system for the study of PARP functions.The PARP1 protein has three functionally defined domains conserved from human to Droso...

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Section: Zn-finger Domain 1 Is Necessary For the Silencing Of Retrotrsupporting

confidence: 81%

Section: Parp C03256mentioning

confidence: 99%

Section: Parp C03256mentioning

confidence: 99%

Section: Parp C03256mentioning

confidence: 99%

See 2 more Smart Citations

Uncoupling of the transactivation and transrepression functions of PARP1 protein

Kotova

Jarnik

Tulin

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…This modification seems to be a conserved mechanism between mammals and Drosophila. Indeed, the Drosophila's hnRNPs Hrb87F, Hrb98DE and Squid have been shown to be associated with pADPr in vivo (Ji and Tulin 2009;Pinnola et al 2007;Ji and Tulin 2013). The Tulin laboratory has shown that Squid and Hrb98DE have a putative pADPr-binding domain, homologous to the pADPr-binding motif identified in human hnRNP M (Ji and Tulin 2009).…”

Section: Post-translational Modifications Of Hnrnps and Their Regulatmentioning

confidence: 99%

Emerging Roles for hnRNPs in post-transcriptional regulation: what can we learn from flies?

2014

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Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a highly conserved family of RNA-binding proteins able to associate with nascent RNAs in order to support their localization, maturation and translation. Research over this last decade has remarked the importance of gene regulatory processes at post-transcriptional level, highlighting the emerging roles of hnRNPs in several essential biological events. Indeed, hnRNPs are key factors in regulating gene expression, thus, having a number of roles in many biological pathways. Moreover, failure of the activities catalysed by hnRNPs affects various biological processes and may underlie several human diseases including cancer, diabetes and neurodegenerative syndromes. In this review, we summarize some of hnRNPs' roles in the model organism Drosophila melanogaster, particularly focusing on their participation in all aspects of post-transcriptional regulation as well as their conserved role and involvement in the aetiology of human pathologies.

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Kinetic Control of One‐Pot Trans‐Splicing Reactions by Using a Wild‐Type and Designed Split Intein

2011

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Keywords ion pairs; protein design; protein-protein interactions; semisynthesisCoulombic forces play an important role in facilitating protein-protein interactions. It has been demonstrated that a strong electrostatic potential between two interacting proteins correlates with a fast rate of association and a strong binding affinity. [1] Indeed, this principle has been exploited to enhance the binding properties of engineered protein interfaces. [2] Nonetheless, little research has focused on utilizing intermolecular ion pairs to modulate specificity in protein-protein interactions. [3][4][5] Naturally split inteins are a potentially interesting system for engineering electrostatically driven specificity, as the formation of a catalytically competent structure requires the association of two oppositely charged protomers. In their endogenous environment, split inteins catalyze protein transsplicing (PTS, Scheme 1) of essential gene fragments, and thus are under evolutionary pressure to associate rapidly with high fidelity and dissociate slowly post-catalysis to prevent the re-formation of unproductive complexes. Out of their native context, split inteins have seen widespread use in a number of biotechnological applications, as a result of their capacity to ligate flanking protein sequences (exteins) in trans. [6] Applications of PTS include segmental isotopic labeling of proteins for NMR spectroscopy, [7] protein immobilization, [8] the labeling of proteins with extrinsic probes, [9] protein and peptide cyclization, [10] and control of protein function. [11,12] Despite the utility of PTS, little is known about what drives efficient association of split intein fragments. Sequence alignments of naturally split inteins show highly conserved charge segregation, with acidic residues concentrated at specific positions on the N-intein and basic residues conserved on the C-intein (N-and C-terminal protomers, Figure 1a). [13] Furthermore, a bioinformatic sequence analysis of the intein family indicates that this charge segregation is significantly more prevalent in naturally split inteins than intact ones ( Figure 1c). Interestingly, when the conserved charged residues are mapped onto the structure determined by NMR spectrocopy of the wild-type DnaE intein from Nostoc punctiforme (Npu WT ), many are found to be participating in intermolecular ion pairs and ion triads (Figure 1b).

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Nucleosomal Core Histones Mediate Dynamic Regulation of Poly(ADP-ribose) Polymerase 1 Protein Binding to Chromatin and Induction of Its Enzymatic Activity

Cited by 102 publications

References 43 publications

Uncoupling of the transactivation and transrepression functions of PARP1 protein

Uncoupling of the transactivation and transrepression functions of PARP1 protein

Emerging Roles for hnRNPs in post-transcriptional regulation: what can we learn from flies?

Kinetic Control of One‐Pot Trans‐Splicing Reactions by Using a Wild‐Type and Designed Split Intein

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