<i>IN VITRO</i> PHOTOREACTIVATION OF ULTRAVIOLET‐INACTIVATED RIBONUCLEIC ACID FROM TOBACCO MOSAIC VIRUS

Hurter, J.; Gordon, Milton P.; Kirwan, J. P.; McLaren, A. D.

doi:10.1111/j.1751-1097.1974.tb06497.x

Cited by 21 publications

(4 citation statements)

References 38 publications

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“…Alternatively, because transcripts exist whose half-lives span several life cycles (Herrick et al, 1990), it might be worth repairing damaged transcripts rather than discarding them. Studies from the 1970s suggested that photoreactivation might repair UV-damaged viral RNA in plants (Merriam and Gordon, 1965;Murphy and Gordon, 1971;Hurter et al, 1974). More recent work showed that alkylation damage to RNA is repaired in vivo both in bacteria and in human cells (Aas et al, 2003;Ougland et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

A Novel Class of mRNA-containing Cytoplasmic Granules Are Produced in Response to UV-Irradiation

Gaillard

Aguilera

2008

MBoC

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Nucleic acids are substrates for different types of damage, but little is known about the fate of damaged RNAs. We addressed the existence of an RNA-damage response in yeast. The decay kinetics of GAL1p-driven mRNAs revealed a dose-dependent mRNA stabilization upon UV-irradiation that was not observed after heat or saline shocks, or during nitrogen starvation. UV-induced mRNA stabilization did not depend on DNA repair, damage checkpoint or mRNA degradation machineries. Notably, fluorescent in situ hybridization revealed that after UV-irradiation, polyadenylated mRNA accumulated in cytoplasmic foci that increased in size with time. In situ colocalization showed that these foci are not processing-bodies, eIF4E-, eIF4G-, and Pab1-containing bodies, stress granules, autophagy vesicles, or part of the secretory or endocytic pathways. These results point to the existence of a specific eukaryotic RNA-damage response, which leads to new polyadenylated mRNA-containing granules (UV-induced mRNA granules; UVGs). We propose that potentially damaged mRNAs, which may be deleterious to the cell, are temporarily stored in UVG granules to safeguard cell viability. INTRODUCTIONDNA repair is crucial to maintain genome integrity, but it is not the only target for nucleic acid-damaging agents, because these may affect RNA molecules as well. In the cell, RNA is more abundant than DNA, and almost all cellular RNAs either encode proteins (mRNA) or are involved in the mechanism of protein production (rRNA and tRNA). Nevertheless, only 28% of genomic DNA is transcribed into RNA, and only 5% of these transcribed sequences actually encode proteins in humans (Baltimore, 2001). Because RNA is mostly single stranded, it may be more susceptible to damaging agents than DNA, in which bases are protected by hydrogen bonding and located inside the double helix (reviewed in Bregeon and Sarasin, 2005). From this point of view, it is likely that significant RNA damage occurs when cells are exposed to genotoxic agents. In fact, alkylating agents, reactive oxygen species, and UV-irradiation have been shown to induce RNA lesions (reviewed in Bregeon and Sarasin, 2005). RNA oxidation has been implied in a variety of neurological disorders (reviewed in Nunomura et al., 2006), whereas some anticancer agents cause RNA damage that lead to cell cycle arrest and cell death as much as DNA damage does (reviewed in Bellacosa and Moss, 2003;Bregeon and Sarasin, 2005). Moreover, nitrogen mustard, cisplatin, and alkylating agents inhibit translation reactions, which indicates that a single mRNA lesion may be sufficient to block translation (Rosenberg and Sato, 1988;Masta et al., 1995;Heminger et al., 1997;Ougland et al., 2004).The abundance of individual mRNAs in the cell is determined by the rate at which they are produced and degraded. mRNA stability can be regulated in response to a variety of stimuli, allowing for rapid alterations in gene expression. Many clinically relevant mRNAs are regulated by differential RNA stability, and the aberrant control of mRNA sta...

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Section: Discussionmentioning

confidence: 99%

A Novel Class of mRNA-containing Cytoplasmic Granules Are Produced in Response to UV-Irradiation

Gaillard

Aguilera

2008

MBoC

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“…It has been shown previously that several DNA repair enzymes acting by direct damage reversal can also repair altered RNA. Thus, ultraviolet light-irradiated tobacco mosaic virus RNA is corrected by a host photoreactivating enzyme in plant leaf cells, catalyzing light-dependent cleavage of uracil dimers to regenerate biological activity of the viral RNA (27). The extensively investigated DNA photolyase from E. coli cleaves cyclobutane pyrimidine dimers not only in DNA, but also in RNA, and "therefore might be considered an RNA photolyase as well" (28).…”

Section: Discussionmentioning

confidence: 99%

Minimal Methylated Substrate and Extended Substrate Range of Escherichia coli AlkB Protein, a 1-Methyladenine-DNA Dioxygenase

Koivisto

Duncan

Lindahl

et al. 2003

Journal of Biological Chemistry

101

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The Escherichia coli AlkB protein, and two human homologs ABH2 and ABH3, directly demethylate 1-methyladenine and 3-methylcytosine in DNA. They couple Fe(II)-dependent oxidative demethylation of these damaged bases to decarboxylation of ␣-ketoglutarate. Here, we have determined the kinetic parameters for AlkB oxidation of 1-methyladenine in poly(dA), short oligodeoxyribonucleotides, nucleotides, and nucleoside triphosphates. Methylated poly(dA) was the preferred AlkB substrate of those tested. The oligonucleotide trimer d(Tp1meApT) and even 5-phosphorylated 1-medAMP were relatively efficiently demethylated, and competed with methylated poly(dA) for AlkB activity. A polynucleotide structure was clearly not essential for AlkB to repair 1-methyladenine effectively, but a nucleotide 5 phosphate group was required. Consequently, 1-me-dAMP(5) was identified as the minimal effective AlkB substrate. The nucleoside triphosphate, 1-medATP, was inefficiently but actively demethylated by AlkB; a reaction with 1-me-ATP was even slower. E. coli DNA polymerase I Klenow fragment could employ 1-medATP as a precursor for DNA synthesis in vitro, suggesting that demethylation of alkylated deoxynucleoside triphosphates by AlkB could have biological significance. Although the human enzymes, ABH2 and ABH3, demethylated 1-methyladenine residues in poly(dA), they were inefficient with shorter substrates. Thus, ABH3 had very low activity on the trimer, d(Tp1meApT), whereas no activity was detected with ABH2. AlkB is known to repair methyl and ethyl adducts in DNA; to extend this substrate range, AlkB was shown to reduce the toxic effects of DNA damaging agents that generate hydroxyethyl, propyl, and hydroxypropyl adducts.Alkylating agents occur in the environment and arise endogenously during cellular metabolism. They damage DNA at multiple sites, and the lesions generated may result in mutagenesis and cell death. The importance of preventing these adverse effects is highlighted by the variety of DNA repair mechanisms that have evolved to remove alkylated bases from DNA. These repair functions are conserved from bacteria to humans. In Escherichia coli, the activities are induced up to 1000-fold (1) in the Ada response (the adaptive response to alkylating agents).3-Methyladenine-DNA glycosylases excise cytotoxic 3-methyladenine and related lesions from DNA in the first step of base excision repair (2). In contrast, suicidal O 6 -methylguanine-DNA methyltransferases directly demethylate the highly mutagenic and toxic lesion O 6 -methylguanine by transferring the methyl group onto a cysteine residue in the protein (3). A third type of DNA repair mechanism specific for alkylated bases was recently resolved. The E. coli AlkB protein (4) and its human homologs, ABH2 and ABH3, oxidize the methyl groups of 1-methyladenine (1-meA) 1 and 3-methylcytosine (3-meC) in DNA to directly regenerate unmodified adenine and cytosine residues. The methyl adduct is released as formaldehyde (5-8). AlkB and its human counterparts are members of the ␣-ketoglutar...

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“…A significant number of these events may result in cell death if they exceed the capacity of repair processes. Photoproduct formation has also been demonstrated in RNA, where uracil dimers are formed by UV irradiation, again as a result of the particular susceptibility of the chromophoric n-electron structures in uracil to W radiation absorbance (Hurter et al, 1974;Kim & Sancar, 1991).…”

Section: The N-electron System and Lifementioning

confidence: 96%

Ultraviolet radiation, evolution and the π-electron system

Cockell

1998

Biological Journal of the Linnean Society

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Ultraviolet radiation is an important natural mutagen. Because of the energetic characteristics, the carbon compounds most susceptible to UV absorbance are those that contain π‐electron systems. The π‐electron configuration is most commonly represented in organic chemistry within aromatic ring structures. An analysis of a wide range of biochemically important processes shows that the susceptibility of this system lies at the heart of almost all UV radiation effects on life. Its disruption accounts for UV radiation‐induced damage in nucleic acids, proteins and lipids. However, throughout the evolution of the biosphere, life has also used the UV absorbance of π‐electron containing compounds to screen out UV radiation, turning their UV absorbance into a protection mechanism. Although UV radiation effects can be analyzed in terms of organism physiology, a more reductionist analysis shows the π‐electron system to be the common chemical determinant in the evolution of UV radiation damage effects and protection strategies in organisms. It reveals an interesting evolutionary story.

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IN VITRO PHOTOREACTIVATION OF ULTRAVIOLET‐INACTIVATED RIBONUCLEIC ACID FROM TOBACCO MOSAIC VIRUS

Cited by 21 publications

References 38 publications

A Novel Class of mRNA-containing Cytoplasmic Granules Are Produced in Response to UV-Irradiation

A Novel Class of mRNA-containing Cytoplasmic Granules Are Produced in Response to UV-Irradiation

Minimal Methylated Substrate and Extended Substrate Range of Escherichia coli AlkB Protein, a 1-Methyladenine-DNA Dioxygenase

Ultraviolet radiation, evolution and the π-electron system

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