Site-Specific Oxidation at GG and GGG Sequences in Double-Stranded DNA by Benzoyl Peroxide as a Tumor Promoter

Kawanishi, Shosuke; Oikawa, Shinji; Murata, Mariko; Tsukitome, Hideyuki; Saito, Isao

doi:10.1021/bi990890z

Cited by 55 publications

(50 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, several lines of evidence suggest that telomeres may act as preferential targets for free radical damage. When telomeric oligonucleotides were exposed to oxidative stress using H 2 O 2 and O 2 Ϫ , DNA damage (i.e., cleavage sites and adducts) preferentially occurred at the 5Ј site of 5Ј-GGG-3Ј sequence in an oligonucleotide (22). Fenton reactions (between H 2 O 2 and Fe 2ϩ ) cause preferential cleavage and strand breaks located at the 5Ј end of the sequence RGGG in a plasmid containing 81-telomere repeats (17).…”

Section: Discussionmentioning

confidence: 99%

Induction of Nitric Oxide Synthase-Dependent Telomere Shortening after Functional Inhibition of Hsp90 in Human Tumor Cells

Compton¹,

Elmore²,

Haydu³

et al. 2006

Molecular and Cellular Biology

View full text Add to dashboard Cite

In most cancer cells, the lengths of telomeres, the functional DNA-protein complexes located at chromosome ends, are maintained by the ribonucleoprotein telomerase. Hsp90 facilitates the assembly of telomerase and remains associated with the functional complex, implying a direct involvement of Hsp90 in telomere length regulation. In an effort to elucidate the effects of Hsp90 inhibition on function and viability of human prostate cancer cells, both pharmacological (radicicol) and genetic (small interfering RNA) approaches were utilized to target Hsp90. Depletion of functional Hsp90 caused dramatic telomere shortening followed by apoptosis. Of particular significance, these cells exhibit a high level of nitric oxide synthase (NOS)-dependent free radical production, and simultaneous treatment of cells with the NOS inhibitor L-NAME resulted in telomere elongation and prevention of apoptosis. In addition, we observe significant DNA damage assessed by telomere dysfunction, although in the absence of a classical DNA damage response. Overall, our data suggest a novel mechanism whereby inhibition of Hsp90 disrupts free radical homeostasis and contributes directly to telomere erosion, further implicating Hsp90 as a potential therapeutic target for cancer cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of Nitric Oxide Synthase-Dependent Telomere Shortening after Functional Inhibition of Hsp90 in Human Tumor Cells

Compton¹,

Elmore²,

Haydu³

et al. 2006

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Many investigations have indicated that catechol strongly enhances cancer development in rats and mice initiated with carcinogen, such as benzo[a]pyrene and N-methyl-N 0 -nitro-N-nitrosoguanidine . Kawanishi et al [1999] have suggested that some tumor promoters act to produce DNA damage, mediated by ROS. Oikawa et al [2001] demonstrated that catechol could induce metal-dependent H 2 O 2 generation, and subsequent damage to DNA fragments obtained from the human p53 and p16 tumor suppressor genes.…”

Section: Catechol and Dna Damage: An Oxidative Pathwaymentioning

confidence: 99%

The role of catechols and free radicals in benzene toxicity: An oxidative DNA damage pathway

Barreto

Madureira

Capani

et al. 2009

Environ and Mol Mutagen

View full text Add to dashboard Cite

Benzene is a widespread volatile compound and an environmental contaminant. Since it causes important toxic effects in workers exposed to low levels, long-term exposure to this compound has been extensively studied. Leukemia, blood disorders, bone marrow depression, and some types of cancer are directly related to benzene-initiated toxicity. Bioactivation of benzene can lead to the formation of hazardous metabolites such as phenol, hydroquinone, and catechol. Catechol forms semiquinones and reactive quinones that are presumed to play an important role in the generation of reactive oxygen species (ROS). ROS formation can directly induce single and double strand breaks in the DNA, oxidized nucleotides, and hyper-recombination, and consequently produces deleterious genetic changes. In this review, we have addressed the cytotoxic effects of benzene and its main metabolite, catechol, focusing on the oxidative pathway and further DNA damage.

show abstract

“…Also, the codons GGG and CCC, corresponding to glycine and proline, are underrepresented. This underrepresentation might be explained by the susceptibility of runs of Gs and Cs to site-specific oxidative damage and also to frameshifting during translation (Janel-Bintz et al 1994;Kawanishi et al 1999). We also investigated the relations among abundant acidic residues in the proteome, codon frequency, and GC composition.…”

Section: Codon Biasmentioning

confidence: 99%

Understanding the Adaptation of Halobacterium Species NRC-1 to Its Extreme Environment through Computational Analysis of Its Genome Sequence

Kennedy¹,

Ng²,

Salzberg³

et al. 2001

Genome Res.

301

267

View full text Add to dashboard Cite

The genome of the halophilic archaeon Halobacterium sp. NRC-1 and predicted proteome have been analyzed by computational methods and reveal characteristics relevant to life in an extreme environment distinguished by hypersalinity and high solar radiation: (1) The proteome is highly acidic, with a median pI of 4.9 and mostly lacking basic proteins. This characteristic correlates with high surface negative charge, determined through homology modeling, as the major adaptive mechanism of halophilic proteins to function in nearly saturating salinity. (2) Codon usage displays the expected GC bias in the wobble position and is consistent with a highly acidic proteome. (3) Distinct genomic domains of NRC-1 with bacterial character are apparent by whole proteome BLAST analysis, including two gene clusters coding for a bacterial-type aerobic respiratory chain. This result indicates that the capacity of halophiles for aerobic respiration may have been acquired through lateral gene transfer. (4) Two regions of the large chromosome were found with relatively lower GC composition and overrepresentation of IS elements, similar to the minichromosomes. These IS-element-rich regions of the genome may serve to exchange DNA between the three replicons and promote genome evolution. (5) GC-skew analysis showed evidence for the existence of two replication origins in the large chromosome. This finding and the occurrence of multiple chromosomes indicate a dynamic genome organization with eukaryotic character.

show abstract

Site-Specific Oxidation at GG and GGG Sequences in Double-Stranded DNA by Benzoyl Peroxide as a Tumor Promoter

Cited by 55 publications

References 39 publications

Induction of Nitric Oxide Synthase-Dependent Telomere Shortening after Functional Inhibition of Hsp90 in Human Tumor Cells

Induction of Nitric Oxide Synthase-Dependent Telomere Shortening after Functional Inhibition of Hsp90 in Human Tumor Cells

The role of catechols and free radicals in benzene toxicity: An oxidative DNA damage pathway

Understanding the Adaptation of Halobacterium Species NRC-1 to Its Extreme Environment through Computational Analysis of Its Genome Sequence

Contact Info

Product

Resources

About