The specific binding of nuclear protein(s) to the cAMP responsive element (CRE) sequence (TGACGTCA) is reduced by the misincorporation of U and increased by the deamination of C

Verri, Annalisa; Mazzarello, Paolo; Biamonti, Giuseppe; Spadari, Silvio; Focher, Federico

doi:10.1093/nar/18.19.5775

Cited by 68 publications

(50 citation statements)

References 21 publications

(21 reference statements)

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“…The absence of the 5-methyl group in uracil has the potential to alter DNA structure and dynamic features that might be important for recognition by transcription factors or other DNA binding proteins (23,25). For example, uracils localized in the origin of replication in HSV-1 were found to perturb the binding of the HSV-1 origin binding protein (27), and incorporated uracils in the cAMP response element (CRE) of rat stomatostatin gene led to a two-to fourfold decrease in binding of CRE binding proteins from HeLa extracts (26). Our observation of reduced GFP expression from the exogenously uracilated DNA in the HT29-Ugi cell line supports the proposal that the presence of uracil in DNA can lead to reduced gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration

Weil

Ghosh²,

Zhou

et al. 2013

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

119

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Significance Misincorporation of dUTP into DNA is detrimental to eukaryotes, prokaryotes, and viruses. This study reveals the fate of uracilated HIV-1 DNA in human cells. Early stages of the viral life cycle are unaffected, but integration of uracilated viral DNA into the host genome is prevented. This effect is wholly dependent on the presence of UNG2, a nuclear enzyme that excises uracil from DNA. This study establishes that UNG2 is a restriction factor for uracilated HIV-1 DNA and explains why this pathway is not fully engaged in CD4+ T cells and macrophages.

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Section: Discussionmentioning

confidence: 99%

Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration

Weil

Ghosh²,

Zhou

et al. 2013

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

119

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“…The presence of uracil in DNA can affect DNA dynamic conformation as well as sequence-specific protein binding (28). Nonetheless, it has been reported that the major measurable consequences of high levels of uracil in DNA are lesions created by the attempt of cells to remove this nucleotide (29).…”

Section: Discussionmentioning

confidence: 99%

Phage φ29 protein p56 prevents viral DNA replication impairment caused by uracil excision activity of uracil-DNA glycosylase

Serrano‐Heras

Bravo

Salas

2008

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

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Protein p56 encoded by the Bacillus subtilis phage 29 inhibits host uracil-DNA glycosylase (UDG) activity. In previous studies, we suggested that this inhibition is likely a defense mechanism developed by phage 29 to prevent the action of UDG if uracilation occurs in DNA either from deamination of cytosine or the incorporation of dUMP during viral DNA replication. In this work, we analyzed the ability of 29 DNA polymerase to insert dUMP into DNA. Primer extension analysis showed that viral DNA polymerase incorporates dU opposite dA with a catalytic efficiency only 2-fold lower than that for dT. Using the 29 DNA amplification system, we found that 29 DNA polymerase is also able to carry out the extension of the dA:dUMP pair and replicate past uracil. Additionally, UDG and apurinic-apyrimidinic endonuclease treatment of viral DNA isolated from 29-infected cells revealed that uracil residues arise in 29 DNA during replication, probably as a result of misincorporation of dUMP by the 29 DNA polymerase. On the other hand, the action of UDG on uracil-containing 29 DNA impaired in vitro viral DNA replication, which was prevented by the presence of protein p56. Furthermore, transfection activity of uracil-containing 29 DNA was significantly higher in cells that constitutively synthesized p56 than in cells lacking this protein. Thus, our data support a model in which protein p56 ensures an efficient viral DNA replication, preventing the deleterious effect caused by UDG when it eliminates uracil residues present in the 29 genome.29 DNA polymerase ͉ DNA repair ͉ protein-primed replication ͉ dUMP incorporation

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“…Moreover, deletion of HCMV UNG delays and diminishes replication of the virus in serum-deprived primary human fibroblasts (10). HSV-1 UNG (UL2 product) was first reported to be dispensable for viral replication in tissue culture (46), but later evidence suggested that the protein is required for virus reactivation from latency and for efficient replication in nerve tissue, which contains very low levels of cellular UNG (19,55,74).…”

mentioning

confidence: 99%

Characterization of the Uracil-DNA Glycosylase Activity of Epstein-Barr Virus BKRF3 and Its Role in Lytic Viral DNA Replication

Huang

Wang

et al. 2007

J Virol

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Uracil-DNA glycosylases (UDGs) of the uracil-N-glycosylase (UNG) family are the primary DNA repair enzymes responsible for removal of inappropriate uracil from DNA. Recent studies further suggest that the nuclear human UNG2 and the UDGs of large DNA viruses may coordinate with their DNA polymerase accessory factors to enhance DNA replication. Based on its amino acid sequence, the putative UDG of Epstein-Barr virus (EBV), BKRF3, belongs to the UNG family of proteins, and it was demonstrated previously to enhance oriLyt-dependent DNA replication in a cotransfection replication assay. However, the expression and enzyme activity of EBV BKRF3 have not yet been characterized. In this study, His-BKRF3 was expressed in bacteria and purified for biochemical analysis. Similar to the case for the Escherichia coli and human UNG enzymes, His-BKRF3 excised uracil from single-stranded DNA more efficiently than from double-stranded DNA and was inhibited by the purified bacteriophage PBS1 inhibitor Ugi. In addition, BKRF3 was able to complement an E. coli ung mutant in rifampin and nalidixic acid resistance mutator assays. The expression kinetics and subcellular localization of BKRF3 products were detected in EBV-positive lymphoid and epithelial cells by using BKRF3-specific mouse antibodies. Expression of BKRF3 is regulated mainly by the immediateearly transcription activator Rta. The efficiency of EBV lytic DNA replication was slightly affected by BKRF3 small interfering RNA (siRNA), whereas cellular UNG2 siRNA or inhibition of cellular and viral UNG activities by expressing Ugi repressed EBV lytic DNA replication. Taking these results together, we demonstrate the UNG activity of BKRF3 in vitro and in vivo and suggest that UNGs may participate in DNA replication or repair and thereby promote efficient production of viral DNA.

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The specific binding of nuclear protein(s) to the cAMP responsive element (CRE) sequence (TGACGTCA) is reduced by the misincorporation of U and increased by the deamination of C

Cited by 68 publications

References 21 publications

Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration

Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration

Phage φ29 protein p56 prevents viral DNA replication impairment caused by uracil excision activity of uracil-DNA glycosylase

Characterization of the Uracil-DNA Glycosylase Activity of Epstein-Barr Virus BKRF3 and Its Role in Lytic Viral DNA Replication

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