Poly (ADP-Ribose) Polymerase 1 Is Required for Protein Localization to Cajal Body

Kotova, Elena; Jarnik, Michael; Tulin, Adrian

doi:10.1371/journal.pgen.1000387

Cited by 74 publications

(88 citation statements)

References 53 publications

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“…We found that PARP Δ300 protein is completely relocalized into nucleoplasmic bodies at the third-instar larvae stage (Fig. 2C), which is a pattern identical to what we had previously shown for full-length PARP1 protein (23). Immunoblot analysis of proteins extracted from parg 27.1 ; parp C03256 doublemutant animals expressing PARP Δ300 -EYFP confirmed that the PARP Δ300 isoform is able to perform a pADPr reaction and could largely automodify itself (Fig.…”

Section: Parp C03256supporting

confidence: 86%

“…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%

“…The negative feedback loop mediated by automodification limits the time during which PARP1 molecules can remain active. In Parg mutants, we previously showed that PARP1 protein is pADPribosylated and removed from chromatin into specific nucleoplasmic bodies (18,23). To test the enzymatic activation of PARP Δ300 and its ability to react to automodification, we expressed the PARP Δ300 -EYFP transgene in parg 27.1 ; parp C03256 double mutants and analyzed PARP Δ300 -EYFP protein dynamics using in vivo imaging.…”

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: Parp C03256supporting

confidence: 86%

Section: Parp C03256mentioning

confidence: 99%

Section: Parp C03256mentioning

confidence: 99%

See 1 more Smart Citation

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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“…92 Poly ADP ribose promotes phase separation, 93 and poly (ADP-ribose) polymerase has been detected in Drosophila HLBs. 94 Finally, given that IDRs might be promiscuous, some proteins might concentrate in the HLB but not have an essential biological or biochemical function in histone mRNA biosynthesis. Such promiscuity may explain the observation that Coilin, which contains regions of low sequence complexity that are likely IDRs, 95 sometimes appears within HLBs but is not required for HLB assembly or for histone mRNA biosynthesis.…”

Section: Does Phase Separation Help Drive Hlb Assembly?mentioning

confidence: 99%

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

2017

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Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These mRNAs end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of the pre-mRNA. The genes for all 5 histone proteins are clustered in all metazoans and coordinately regulated with high levels of expression during S phase. Production of histone mRNAs occurs in a nuclear body called the Histone Locus Body (HLB), a subdomain of the nucleus defined by a concentration of factors necessary for histone gene transcription and premRNA processing. These factors include the scaffolding protein NPAT, essential for histone gene transcription, and FLASH and U7 snRNP, both essential for histone pre-mRNA processing. Histone gene expression is activated by Cyclin E/Cdk2-mediated phosphorylation of NPAT at the G1-S transition. The concentration of factors within the HLB couples transcription with pre-mRNA processing, enhancing the efficiency of histone mRNA biosynthesis. KEYWORDSCell cycle; Drosophila; histone genes; mRNA processing; nuclear bodyProper utilization of genetic information in eukaryotes requires extensive three-dimensional organization of the genome and its associated proteins within the nucleus. The basic unit of genome organization is the nucleosome, an octamer of two molecules of each of the four core histone proteins (H2A, H2B, H3 and H4) that packages »147 base pairs of DNA. In mammalian cells, approximately 4£10 8 molcules of each core histone must be synthesized during S phase of the cell cycle to package the newly replicated DNA. Defects in this process result in genome instability that can contribute to human pathologies like cancer. Histone protein synthesis results from a large increase in production at the beginning of S phase of equal amounts of mRNAs encoding the four core nucleosomal histones, as well as histone H1. This highly coordinated gene expression event is performed by a set of transcription and pre-mRNA processing factors unique to replication dependent (RD) histone mRNA biosynthesis that assemble into a nuclear body tightly associated with RD histone genes called the histone locus body (HLB). HLB formation involves a combination of ordered and stochastic assembly steps, and cell cycle regulated changes in the HLB occur to activate histone gene expression during S phase. Here we describe the history of how the HLB was discovered followed by a discussion of HLB assembly mechanism and how the HLB functions in RD histone mRNA biosynthesis.

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“…19,[95][96][97][98][99] All these regulatory functions can be achieved via the basic enzymatic activity of PARP1, which is involved in post-translational modification of specific proteins. PARP1 catalyzes the attachment of multiple chains of ADP ribose [poly (ADP) ribose; PAR] from NAD to target (acceptor) proteins, and the main acceptor is PARP1 protein itself.…”

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confidence: 99%

Cajal bodies and their role in plant stress and disease responses

et al. 2016

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Cajal bodies (CBs) are distinct sub-nuclear structures that are present in eukaryotic living cells and are often associated with the nucleolus. CBs play important roles in RNA metabolism and formation of RNPs involved in transcription, splicing, ribosome biogenesis, and telomere maintenance. Besides these primary roles, CBs appear to be involved in additional functions that may not be directly related to RNA metabolism and RNP biogenesis. In this review, we assess possible roles of plant CBs in RNA regulatory pathways such as nonsense-mediated mRNA decay and RNA silencing. We also summarize recent progress and discuss new non-canonical functions of plant CBs in responses to stress and disease. It is hypothesized that CBs can regulate these responses via their interaction with poly(ADP ribose)polymerase (PARP), which is known to play an important role in various physiological processes including responses to biotic and abiotic stresses. It is suggested that CBs and their components modify PARP activities and functions.

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Poly (ADP-Ribose) Polymerase 1 Is Required for Protein Localization to Cajal Body

Cited by 74 publications

References 53 publications

Uncoupling of the transactivation and transrepression functions of PARP1 protein

Uncoupling of the transactivation and transrepression functions of PARP1 protein

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

Cajal bodies and their role in plant stress and disease responses

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