The Guanine-Quadruplex Structure in the Human c-myc Gene's Promoter Is Converted into B-DNA Form by the Human Poly(ADP-Ribose)Polymerase-1

Fekete, Anna; Kenesi, Erzsébet; Hunyadi‐Gulyás, Éva; Dürgő, Hajnalka; Berko, Barbara; Dunai, Zsuzsanna A.; Bauer, Paul

doi:10.1371/journal.pone.0042690

Cited by 39 publications

(21 citation statements)

References 71 publications

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“…This structure, which is in equilibrium with the double-stranded B-DNA form, prevents the binding of transcriptional activators [33]. Interestingly, it has been previously reported that PARP-1 binds to this sequence in vitro [34] and that this binding accelerates the in vitro conversion of the c-MYC GQ structure into its B-DNA form [35]. Our ChIP assays revealed that the enzyme also binds to an adjacent region, which contains that CT-I 2 element that has been previously recognized as biologically relevant for c-MYC transcription.…”

Section: Discussionmentioning

confidence: 98%

Poly(ADP-Ribosyl)ation Is Required to Modulate Chromatin Changes at c-MYC Promoter during Emergence from Quiescence

et al. 2014

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Poly(ADP-ribosyl)ation is a post-translational modification of various proteins and participates in the regulation of chromatin structure and transcription through complex mechanisms not completely understood. We have previously shown that PARP-1, the major family member of poly(ADP-ribose)polymerases, plays an important role in the cell cycle reactivation of resting cells by regulating the expression of Immediate Early Response Genes, such as c-MYC, c-FOS, JUNB and EGR-1. In the present work we have investigated the molecular mechanisms by which the enzyme induces c-MYC transcription upon serum stimulation of quiescent cells. We show that PARP-1 is constitutively associated in vivo to a c-MYC promoter region recognized as biologically relevant for the transcriptional regulation of the gene. Moreover, we report that serum stimulation causes the prompt accumulation of ADP-ribose polymers on the same region and that this modification is required for chromatin decondensation and for the exchange of negative for positive transcriptional regulators. Finally we provide evidence that the inhibition of PARP activity along with serum stimulation impairs c-MYC induction by preventing the proper accumulation of histone H3 phosphoacetylation, a specific chromatin mark for the activation of Immediate Early Response Genes. These findings not only suggest a novel strategy by which PARP-1 regulates the transcriptional activity of promoters but also provide new information about the complex regulation of c-MYC expression, a critical determinant of the transition from quiescence to proliferation.

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Section: Discussionmentioning

confidence: 98%

Poly(ADP-Ribosyl)ation Is Required to Modulate Chromatin Changes at c-MYC Promoter during Emergence from Quiescence

et al. 2014

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“…Although there is a lot known about G4 structure formation and its impact on c-MYC transcription, only little is known about the 'disruption' of these G4 structures. So far, only three proteins, among them one helicase, have been described to support unfolding of G4 structures in c-MYC: CNBP, PARP-1, and Pif1 [99][100][101]. Nevertheless, a detailed analysis of these proteins and changes in G4-mediated c-MYC transcription are missing.…”

Section: Effects Of Helicases Acting On G4 Structures During Transcrimentioning

confidence: 99%

G-quadruplex unwinding helicases and their function in vivo

Sauer

Paeschke

2017

Biochemical Society Transactions

153

146

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The concept that G-quadruplex (G4) structures can form within DNA or RNA has been long known and extensively discussed. In recent years, accumulating evidences imply that G-quadruplex structures form Initially, inefficient regulation of G-quadruplex structures was mainly associated with genome instability. However, due to the location of G-quadruplex motifs and their evolutionary conservation, different cellular functions of these structures have been postulated (e.g. in telomere maintenance, DNA replication, transcription, and translation). Regardless of their function, efficient and controlled formation and unwinding are very important, because 'mis'-regulated G-quadruplex structures are detrimental for a given process, causing genome instability and diseases. Several helicases have been shown to target and regulate specific G-quadruplex structures. This mini-review focuses on the biological consequences of G4 disruption by different helicases .

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“…Both enzymes may, in addition, contribute to cancer progression, regulating the expression of critical genes. PARP-1 may stimulate transcription of the c-MYC gene, by converting the guanine-quadruplex structure in the human c-MYC gene's promoter into B-DNA, and thus facilitating access to this promoter for transcription factors [9] . OGG1, in turn, facilitates transcription of genes regulated by c-MYC.…”

Section: Introductionmentioning

confidence: 99%

PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1

et al. 2014

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The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo) level in leukocyte DNA of healthy controls (138 individuals), patients with benign adenomas (AD, 137 individuals) and with malignant carcinomas (CRC, 169 individuals) revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.

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The Guanine-Quadruplex Structure in the Human c-myc Gene's Promoter Is Converted into B-DNA Form by the Human Poly(ADP-Ribose)Polymerase-1

Cited by 39 publications

References 71 publications

Poly(ADP-Ribosyl)ation Is Required to Modulate Chromatin Changes at c-MYC Promoter during Emergence from Quiescence

Poly(ADP-Ribosyl)ation Is Required to Modulate Chromatin Changes at c-MYC Promoter during Emergence from Quiescence

G-quadruplex unwinding helicases and their function in vivo

PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1

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