A single 8,5′-cyclo-2′-deoxyadenosine lesion in a TATA box prevents binding of the TATA binding protein and strongly reduces transcription in vivo

Marietta, Cheryl A.; Gulam, Huzaefah; Brooks, Philip J.

doi:10.1016/s1568-7864(02)00148-9

Cited by 66 publications

(49 citation statements)

References 39 publications

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“…We also demonstrated that the presence of a cyclopurine-deoxynucleoside lesion in a transcription factor binding site can block transcription factor binding, and inhibit gene expression in XP cells (Marietta et al, 2002), illustrating another mechanism by which these lesions can reduce gene expression.…”

Section: Cyclopurine-deoxynucleosides Are Not Substrates For Other Dnmentioning

confidence: 70%

“…Indeed, the evidence that the NER pathway does not function in non-transcribed DNA in at least some terminally differentiated cells, including neuronal cells (Nouspikel and Hanawalt, 2002), raises the possibility that cyclopurine-deoxynucleosides might accumulate in non-transcribed DNA with aging. We have shown that cyclopurine-deoxynucleoside lesions can prevent transcription factors from binding to their target DNA sequences (Marietta et al, 2002 and manuscript in preparation), illustrating one mechanism by which unrepaired cyclopurine-deoxynucleosides in non-transcribed DNA could impair gene expression and degrade neuronal function over time. Such effects may well be of significance for the decline in neuronal function during human aging (Long et al, 1999).…”

Section: Are Cyclopurine-deoxynucleosides Relevant For Individuals Wimentioning

confidence: 92%

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The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

Brooks

2007

Neuroscience

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112

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Patients with the genetic disease xeroderma pigmentosum (XP) lack the capacity to carry out a specific type of DNA repair process called nucleotide excision repair (NER). The NER pathway plays a critical role in the repair of DNA damage resulting from UV radiation. A subset of XP patients develop a profound neurodegenerative condition known as XP neurological disease. Robbins and colleagues (PNAS 75:1984(PNAS 75: -88, 1978 hypothesized that since UV light cannot reach into the human brain, XP neurological disease results from some form of endogenous DNA damage that is normally repaired by the NER pathway. In the absence of NER, the damage accumulates, causing neuronal death by blocking transcription. In this manuscript, I consider the evidence that a particular class of oxidative DNA lesions, the 8, 5'-cyclopurine-2'-deoxynucleosides, fulfills many of the criteria expected of neurodegenerative DNA lesions in XP. Specifically, these lesions are chemically stable, endogenous DNA lesions that are repaired by the NER pathway but not by any other known process, and strongly block transcription by RNA polymerase II in cells from XP patients. A similar set of criteria might be used to evaluate other candidate DNA lesions responsible for neurological diseases resulting from defects in other DNA repair mechanisms as well.

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Section: Cyclopurine-deoxynucleosides Are Not Substrates For Other Dnmentioning

confidence: 70%

Section: Are Cyclopurine-deoxynucleosides Relevant For Individuals Wimentioning

confidence: 92%

The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

Brooks

2007

Neuroscience

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112

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“…Other factors account for the tissuespecific nature of the type of DNA damage, and its tendency, along with that of c-Myc, to promote neoplastic progression (Vafa et al, 2002;Karlsson et al, 2003) Regulation of ROS and c-Myc function by Prdx1 RA Egler et al contrast, little is known about the biological effects of cyclopurine-2 0 -deoxynucleosides. Recent studies have provided evidence that (5 0 S)-cdA is a cytotoxic lesion, as it was shown to impose a strong block to elongating DNA and RNA polymerases as well as to block the binding of transcription factors to their cognate recognition sequences (Brooks et al, 2000;Kuraoka et al, 2000Kuraoka et al, , 2001Marietta et al, 2002). By inference, (5 0 R)-cdA, (5 0 R)-cdG, and (5 0 S)-cdG may also represent cytotoxic lesions.…”

Section: Discussionmentioning

confidence: 99%

Regulation of reactive oxygen species, DNA damage and c-Myc function by peroxiredoxin 1

et al. 2005

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Overexpression of c-Myc results in transformation and multiple other phenotypes, and is accompanied by the deregulation of a large number of target genes. We previously demonstrated that peroxiredoxin 1 (Prdx1), a scavenger of reactive oxygen species (ROS), interacts with a region of the c-Myc transcriptional regulatory domain that is essential for transformation. This results either in the suppression or enhancement of some c-Myc functions and in the altered expression of select target genes. Most notably, c-Myc-mediated transformation is inhibited, implying a tumor suppressor role for Prdx1. Consistent with this, prdx1À/À mice develop age-dependent hemolytic anemias and/or malignancies. We now show that erythrocytes and embryonic fibroblasts from these animals contain higher levels of ROS, and that the latter cells show evidence of c-Myc activation, including the ability to be transformed by a ras oncogene alone. In contrast, other primary cells from prdx1À/À mice do not have elevated ROS, but nonetheless show increased oxidative DNA damage. This apparent paradox can be explained by the fact that ROS localize primarily to the cytoplasm of prdx1 þ / þ cells, whereas in prdx1À/À cells, much higher levels of nuclear ROS are seen. We suggest that increased DNA damage and tumor susceptibility in prdx1À/À animals results from this shift in intracellular ROS. prdx1À/À mice should be useful in studying the role of oxidative DNA damage in the causation of cancer and its prevention by antioxidants. They should also help in studying the relationship between oncogenes such as c-Myc and DNA damage.

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“…The construction and purification of plasmids containing single lesions, cell culture and transfections were carried out as described by Marietta et al (2002).…”

Section: Methodsmentioning

confidence: 99%

Transcriptional bypass of bulky DNA lesions causes new mutant RNA transcripts in human cells

Marietta

Brooks

2007

EMBO Reports

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Here, we characterize the mutant transcripts resulting from bypass of an 8,5 0 -cyclo-2 0 -deoxyadenosine (cyclo-dA) or cyclobutane pyrimidine dimer (CPD) by human RNA polymerase II (Pol II) in vivo. With the cyclo-dA lesion, we observed two new types of mutant transcripts. In the first type, the polymerase inserted uridine opposite the lesion and then misincorporated adenosine opposite the template deoxyadenosine downstream (5 0 ) of the lesion. The second type contained deletions of 7, 13 or 21 nucleotides (nt) after uridine incorporation opposite the lesion. The frequency of the different types of transcript from the cyclo-dA lesion in mutant human cell lines suggests that the Cockayne syndrome B protein affects the probability of deletion transcript formation. With the CPD-containing construct, we also detected rare transcripts containing 12 nt deletions. These results indicate that RNA pol II in living human cells can bypass helixdistorting DNA lesions that are substrates for nucleotide excision repair, resulting in transcriptional mutagenesis.

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A single 8,5′-cyclo-2′-deoxyadenosine lesion in a TATA box prevents binding of the TATA binding protein and strongly reduces transcription in vivo

Cited by 66 publications

References 39 publications

The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

Regulation of reactive oxygen species, DNA damage and c-Myc function by peroxiredoxin 1

Transcriptional bypass of bulky DNA lesions causes new mutant RNA transcripts in human cells

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