RNA polymerase II bypasses 8-oxoguanine in the presence of transcription elongation factor TFIIS

Kuraoka, Isao; Suzuki, Kyoko; Ito, Shinsuke; Hayashida, Mika; Kwei, Joan Seah Mei; Ikegami, Takahisa; Handa, Hiroshi; Nakabeppu, Yusaku; Tanaka, Kiyoji

doi:10.1016/j.dnarep.2007.01.014

Cited by 81 publications

(78 citation statements)

References 35 publications

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“…Previous reports using cell-free systems have indicated that Ϸ8% of transcripts generated by elongation past 8OG are mutant (31), with the majority containing a C opposite the template lesion (12), in agreement with the data presented here. Interestingly, sequence analysis of truncated transcripts arising from RNAP pausing at the site of damage also indicates that the insertion of A occurs only approximately 8% of the time (32), suggesting that these transcripts are likely to be eventually elongated to full-length, in agreement with data provided by single initiation transcription reactions (29). This bias toward nonmutagenic C insertion, however, could be influenced by the sequence context flanking the lesion.…”

Section: Discussionsupporting

confidence: 62%

“…It is difficult to imagine how 8OG might initiate TCR, because one requirement for this process is thought to be arrest of RNAP at the lesion site, and multiple laboratories using various systems have demonstrated that transcription past 8OG leads to a small population of truncated transcripts in the context of abundant full-length transcripts (11,12,28,29). The level of RNAP pausing can be influenced by various factors, including the sequence context and promoter strength (30), distance of the lesion from the transcription start site (30,31), the relative abundance of CTP and ATP in the reaction (12,29), and the presence of various elongation factors (31,32), but ultimately full-length transcripts are produced. Nevertheless, there is evidence for involvement of Csb in the global repair of 8OG, particularly when combined with the absence of Ogg1 (21, 22), and there is some suggestion that this role is independent of TCR (21).…”

Section: Discussionmentioning

confidence: 99%

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8-Oxoguanine-mediated transcriptional mutagenesis causes Ras activation in mammalian cells

Saxowsky¹,

Meadows²,

Klungland

et al. 2008

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

114

136

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DNA repair ͉ MAP kinase ͉ Csb ͉ transcription-coupled repair ͉ tumorigenesis C ells use numerous mechanisms to neutralize various reactive species before they can damage DNA, as well as overlapping pathways to repair the damage, thus protecting genomic integrity. DNA damage can result in a number of potential outcomes for a mammalian cell (1), including permanent fixation of the damage during replication, leading to a heritable mutation. Replication-centric models of mutagenesis have provided valuable information regarding routes of mutagenesis under conditions of continuous cell growth and replication. These models, however, largely ignore transcription, the other major nucleic acid transaction essential to the cell. In slowly growing or nondividing cells, in which DNA replication is greatly diminished or altogether absent (e.g., terminally differentiated mammalian cells [2]), transcription must continue to provide the cell with the proteins necessary for normal physiologic processes. As such, the interaction of DNA damage with the transcription machinery occurs more frequently than with the replication apparatus.Many types of DNA damage are repaired with greater efficiency if they occur in the template strand of a transcribed gene rather than the nontemplate strand or a nontranscribed region of the genome (3, 4). Bulky lesions that distort the DNA helix will arrest RNA polymerase (RNAP) at the site of damage, promoting transcription-coupled repair (TCR) and allowing the generation of full-length, normal transcripts (5, 6). However, frequently occurring nonbulky lesions, such as 8-oxoguanine

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

8-Oxoguanine-mediated transcriptional mutagenesis causes Ras activation in mammalian cells

Saxowsky¹,

Meadows²,

Klungland

et al. 2008

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

114

136

View full text Add to dashboard Cite

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“…There is strong evidence that stalled RNAP II at bulky adducts activates the TC-NER pathway (36). However, the extent to which oxidized bases block transcription is unclear, with differing results depending not only on the nature of the lesion but also on the transcription system used (30,33,37,38) and possibly on the sequence context of the lesion.…”

Section: Discussionmentioning

confidence: 99%

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

Banerjee

Mandal

Das

et al. 2011

Journal of Biological Chemistry

128

150

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Preferential repair of bulky DNA adducts from the transcribed genes via nucleotide excision repair is well characterized in mammalian cells. However, definitive evidence is lacking for similar repair of oxidized bases, the major endogenous DNA lesions. Here we show that the oxidized base-specific human DNA glycosylase NEIL2 associates with RNA polymerase II and the transcriptional regulator heterogeneous nuclear ribonucleoprotein-U (hnRNP-U), both in vitro and in cells. NEIL2 immunocomplexes from cell extracts preferentially repaired the mutagenic cytosine oxidation product 5-hydroxyuracil in the transcribed strand. In a reconstituted system, we also observed NEIL2-initiated transcription-dependent base excision repair of 5-hydroxyuracil in the transcribed strand, with hnRNP-U playing a critical role. Chromatin immunoprecipitation/reimmunoprecipitation studies showed association of NEIL2, RNA polymerase II, and hnRNP-U on transcribed but not on transcriptionally silent genes. Furthermore, NEIL2-depleted cells accumulated more DNA damage in active than in silent genes. These results strongly support the preferential role of NEIL2 in repairing oxidized bases in the transcribed genes of mammalian cells.

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“…1C). In such cases, excision repair (NER and BER) can participate in removing the DNA lesions because there is a template for DNA repair synthesis in genomic DNA in the G0 phase (19)(20)(21).…”

Section: When Rna Polymerases Encounter Dna Lesionsmentioning

confidence: 99%

When and Where Polymerases Encounter DNA Lesions

Kuraoka

2012

Genes and Environment

Self Cite

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Although there are some similarities and dissimilarities between DNA and RNA polymerase as enzymes, when polymerase encounters a DNA lesion, the polymerase proceeds with one of two actions. One is to stall at the DNA lesion, which results in DNA repair mechanisms or cell death being induced. The other is for the polymerase to bypass the DNA lesion, which results in a mutation that could subsequently lead to carcinogenesis. The eŠects of DNA lesions, on either DNA polymerases or RNA polymerases, might be dependent on the cell cycle. This is because DNA polymerase in replication and RNA polymerase in transcription operate in the S phase and the G0 phase of the cell cycle in human cells, respectively. In addition, lesions may vary in their eŠects among the many cell types in the human body. Most diŠerentiated cells, like cardiomyocytes and neurons, are post-mitotic, non-dividing cells. Some somatic cells, stem cells, and cancer cells are dividing cells in which DNA replication occurs in the S phase. To re-evaluate the biological risk conveyed by DNA lesions in living human cells, studies on cell-cycle-dependent actions of both DNA polymerase and RNA polymerase on DNA templates that contain lesions might be required.

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RNA polymerase II bypasses 8-oxoguanine in the presence of transcription elongation factor TFIIS

Cited by 81 publications

References 35 publications

8-Oxoguanine-mediated transcriptional mutagenesis causes Ras activation in mammalian cells

8-Oxoguanine-mediated transcriptional mutagenesis causes Ras activation in mammalian cells

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

When and Where Polymerases Encounter DNA Lesions

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