DNA Damage by Nitric Oxide

Tamir, Snait; Burney, Samar; Tannenbaum, Steven R.

doi:10.1021/tx9600311

Cited by 239 publications

(163 citation statements)

References 54 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…In fact, overlapping functions of Fpg and NER have also been suggested by other studies (Kow et al, 1990;Asad et al, 2000). Deamination of guanine to xanthine can also result in depurination to form abasic sites in DNA (Tamir et al, 1996), which could be substrates for NER (Lin & Sancar, 1989). These observations support our findings on the sensitivity of NER-deficient bacteria to H 2 O 2 .…”

Section: Discussionsupporting

confidence: 91%

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

et al. 2008

View full text Add to dashboard Cite

Mycobacteria are an important group of human pathogens. Although the DNA repair mechanisms in mycobacteria are not well understood, these are vital for the pathogen's persistence in the host macrophages. In this study, we generated a null mutation in the uvrB gene of Mycobacterium smegmatis to allow us to compare the significance of the nucleotide excision repair (NER) pathway with two important base excision repair pathways, initiated by uracil DNA glycosylase (Ung) and formamidopyrimidine DNA glycosylase (Fpg or MutM), in an isogenic strain background. The strain deficient in NER was the most sensitive to commonly encountered DNAdamaging agents such as UV, low pH, reactive oxygen species, hypoxia, and was also sensitive to acidified nitrite. Taken together with previous observations on NER-deficient M. tuberculosis, these results suggest that NER is an important DNA repair pathway in mycobacteria.

show abstract

Section: Discussionsupporting

confidence: 91%

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Furthermore, NO concentrations in the micromolar range were shown to generate single-stranded DNA breaks. 59,60 It is thus likely that activation of ATR in NOtreated cells occurs in response to the introduction of singlestranded DNA breaks. As shown here, NO strongly promotes the nuclear retention of p53, even under conditions where p53 is otherwise mostly cytoplasmic.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation

2003

View full text Add to dashboard Cite

Nitric oxide (NO) is a potent activator of the p53 tumor suppressor protein. However, the mechanisms underlying p53 activation by NO have not been fully elucidated. We previously reported that a rapid downregulation of Mdm2 by NO may contribute to the early phase of p53 activation. Here we show that NO promotes p53 nuclear retention and inhibits Mdm2-mediated p53 nuclear export. NO induces phosphorylation of p53 on serine 15, which does not require ATM but rather appears to depend on the ATM-related ATR kinase. An ATRkinase dead mutant or caffeine, which blocks the kinase activity of ATR, effectively abolishes the ability of NO to cause p53 nuclear retention, concomitant with its inhibition of p53 serine 15 phosphorylation. Of note, NO enhances markedly the ability of low-dose ionizing radiation to elicit apoptotic killing of neuroblastoma cells expressing cytoplasmic wild-type p53. These findings imply that, through augmenting p53 nuclear retention, NO can sensitize tumor cells to p53-dependent apoptosis. Thus, NO donors may potentially increase the efficacy of radiotherapy for treatment of certain types of cancer.

show abstract

“…This balance between vasodilatory and cytotoxic effects is likely to be very variable as sensitivity to the cytotoxic/antiproliferative effects of NO ¼ have been shown to differ by a factor of 10 between tumour cell lines. 11 The mechanisms responsible for cell death resulting from NO ¼ production are complex, but involve the formation of peroxynitrite, 22 nitrosating agents such as N 2 O 3 23 or nitroxyl; 24 the concentrations required are probably in the 3-10 mm range as shown for the production of DNA single strand breaks. 22 In the present study the cytotoxic effects of NO ¼ were evident in both the in vitro and in vivo systems.…”

Section: Discussionmentioning

confidence: 99%

“…11 The mechanisms responsible for cell death resulting from NO ¼ production are complex, but involve the formation of peroxynitrite, 22 nitrosating agents such as N 2 O 3 23 or nitroxyl; 24 the concentrations required are probably in the 3-10 mm range as shown for the production of DNA single strand breaks. 22 In the present study the cytotoxic effects of NO ¼ were evident in both the in vitro and in vivo systems. In vitro 30% of the cells were killed by prolonged expression of iNOS in the CMV/iNOS group (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Tumour cell radiosensitization using constitutive (CMV) and radiation inducible (WAF1) promoters to drive the iNOS gene: a novel suicide gene therapy

et al. 2002

View full text Add to dashboard Cite

show abstract

DNA Damage by Nitric Oxide

Cited by 239 publications

References 54 publications

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation

Tumour cell radiosensitization using constitutive (CMV) and radiation inducible (WAF1) promoters to drive the iNOS gene: a novel suicide gene therapy

Contact Info

Product

Resources

About