CPD damage recognition by transcribing RNA polymerase II

Brueckner, Florian; Hennecke, Ulrich; Carell, Thomas; Cramer, Patrick

doi:10.1107/s0108767307097073

Cited by 36 publications

(70 citation statements)

References 1 publication

(1 reference statement)

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“…Several studies have characterized the behavior of RNAP when it encounters a bulky lesion during the transcription elongation process (Table 1). Here we will focus on the mechanism of transcription arrest at two bulky lesions repaired by TCR, CPDs and cisplatin-induced intrastrand crosslinks, based on the recent resolution of the crystal structure of Saccharomyces cerevisiae RNAPII arrested at a T<>T CPD or at a cisplatin-induced (1,2 GG) intrastrand crosslink [68,69]. Review articles describing the behavior of prokaryotic and eukaryotic RNA polymerases at several different adducts have recently been published [6, 15,67].…”

Section: Rna Polymerase Arrest At Dna Lesionsmentioning

confidence: 99%

“…It is likely that the presence of a CPD in the transcribed strand affects formation of the RNA:DNA hybrid, and this in turn may shift the equilibrium from nucleotide addition toward arrest. With the resolution of the crystal structure of Saccharomyces cerevisiae RNAPII arrested at a T<>T CPD located in the template strand, new details on the mechanism of transcription arrest at a CPD have been revealed [68] (Fig. 2a).…”

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

“…2a). These studies have shown that RNAPII can correctly incorporate AMP opposite the 3' thymine of the CPD [68,78], but incorporation of the next nucleotide, opposite the 5' thymine of the CPD is a very slow process that can only occur if UMP is misincorporated. This, in turn, causes RNAP to become arrested [68].…”

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

“…These studies have shown that RNAPII can correctly incorporate AMP opposite the 3' thymine of the CPD [68,78], but incorporation of the next nucleotide, opposite the 5' thymine of the CPD is a very slow process that can only occur if UMP is misincorporated. This, in turn, causes RNAP to become arrested [68]. The CPD 5' thymine adopts a wobble position with respect to the base in the undamaged complex, where base pairing can only occur with the wrong nucleotide, due to the unusual position of this base in the catalytic site of the polymerase [68].…”

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

“…This, in turn, causes RNAP to become arrested [68]. The CPD 5' thymine adopts a wobble position with respect to the base in the undamaged complex, where base pairing can only occur with the wrong nucleotide, due to the unusual position of this base in the catalytic site of the polymerase [68]. In fact, the CPD 3' thymine occupies the same position as in the undamaged elongation complex, whereas the CPD 5' thymine is tilted by~40 o with the O4 atom at the location normally occupied by the N3 atom.…”

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

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DNA Repair in Mammalian Cells

Tornaletti

2009

Cell. Mol. Life Sci.

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Arrest of transcription at sites of DNA damage represents a strong signal for apoptosis. To overcome the impasse represented by transcription complexes arrested at sites of damage, cells have evolved a specialized nucleotide excision repair (NER) pathway called transcription-coupled DNA repair (TCR), dedicated to removal of transcription-blocking lesions from the genome. This repair pathway was discovered in Phil Hanawalt's laboratory 20 years ago, but the mechanistic details are still subject of intense research. This article will review the recent literature on the subject with emphasis on how lesions affect the elongation step of transcription and how the initial steps of TCR occur in human cells. (Part of a Multi-author Review).

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Section: Rna Polymerase Arrest At Dna Lesionsmentioning

confidence: 99%

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

Section: Cyclobutane Pyrimidine Dimersmentioning

confidence: 99%

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DNA Repair in Mammalian Cells

Tornaletti

2009

Cell. Mol. Life Sci.

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Transcriptional mutagenesis and its potential roles in the etiology of cancer and bacterial antibiotic resistance

Morreall

Petrova

Doetsch

2013

Journal Cellular Physiology

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Most cells do not undergo continuous cell division and DNA replication, yet they can still acquire novel RNA mutations that can result in the production of mutant proteins and induce a phenotypic change. All cells are frequently subjected to genotoxic insults that give rise to damaged nucleotides which, similarly to DNA replication, can undergo base mispairing during transcription. This mutagenic lesion bypass by RNA polymerase, transcriptional mutagenesis (TM), has been studied in a variety of systems and organisms, and may be involved in diverse pathogenic processes, such as tumorigenesis and the acquisition of bacterial antibiotic resistance. Tumor cells and bacteria within the human body are subject to especially high levels of oxidative stress, which can damage DNA and consequently drive TM. Mutagenesis at the level of transcription may allow cells to escape growth arrest and undergo replication that could permanently establish mutations in DNA in a process called retromutagenesis (RM). Here, we review the broad range of DNA damages which may result in TM including a variety of non-bulky lesions and some bulky lesions, which recent studies indicate may not completely block transcription, and emerging evidence supporting the RM concept in the context of tumorigenesis and antibiotic resistance.

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Functional Architecture of RNA Polymerase I

Kuhn

Geiger

Baumli

et al. 2007

Cell

194

334

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Synthesis of ribosomal RNA (rRNA) by RNA polymerase (Pol) I is the first step in ribosome biogenesis and a regulatory switch in eukary-otic cell growth. Here we report the 12 A ˚ cryo-electron microscopic structure for the complete 14-subunit yeast Pol I, a homology model for the core enzyme, and the crystal structure of the subcomplex A14/43. In the resulting hybrid structure of Pol I, A14/43, the clamp, and the dock domain contribute to a unique surface interacting with promoter-specific initiation factors. The Pol I-specific subunits A49 and A34.5 form a heterodimer near the enzyme funnel that acts as a built-in elongation factor and is related to the Pol II-associated factor TFIIF. In contrast to Pol II, Pol I has a strong intrinsic 3 0-RNA cleavage activity, which requires the C-terminal domain of subunit A12.2 and, apparently, enables ribosomal RNA proofreading and 3 0-end trimming.

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CPD damage recognition by transcribing RNA polymerase II

Abstract: This copy is for your personal, non-commercial

Cited by 36 publications

References 1 publication

DNA Repair in Mammalian Cells

DNA Repair in Mammalian Cells

Transcriptional mutagenesis and its potential roles in the etiology of cancer and bacterial antibiotic resistance

Functional Architecture of RNA Polymerase I

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