Hereditary Photodermatoses

Oh, Dennis H.; Spivak, Graciela

doi:10.1007/978-1-4419-6448-9_9

Cited by 5 publications

(5 citation statements)

References 44 publications

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“…Defects in NER that occur in the hereditary disease, xeroderma pigmentosum, result in mutations to key tumor suppressor and oncogenes and a significantly increased incidence of skin cancers, including SCCs . NER comprises two subpathways: Global genomic repair (GGR) removes lesions in all DNA domains and is critical to suppress photocarcinogenesis, and transcription‐coupled repair, which preferentially removes lesions from transcribed strands of actively expressed genes, is specifically defective in the diseases Cockayne syndrome, photosensitive forms of trichothiodystrophy and UV sensitive syndrome, none of which are prone to photocarcinogenesis .…”

Section: Introductionmentioning

confidence: 99%

Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells

Dong

Ona

Scandurra

et al. 2016

Photochem & Photobiology

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Squamous cell carcinomas (SCCs) are associated with ultraviolet radiation and multiple genetic changes, but the mechanisms leading to genetic instability are unclear. SCC cell lines were compared to normal keratinocytes for sensitivity to ultraviolet radiation, DNA repair kinetics and DNA repair protein expression. Relative to normal keratinocytes, four SCC cell lines were all variably sensitive to ultraviolet radiation and, except for the SCC25 cell line, were deficient in global repair of cyclobutane pyrimidine dimers, although not 6-4 photoproducts. Impaired DNA repair of cyclobutane pyrimidine dimers was associated with reduced mRNA expression from XPC but not DDB2 genes which each encode key DNA damage recognition proteins. However, levels of XPC or DDB2 proteins or both were variably reduced in repair-deficient SCC cell lines. p53 levels did not correlate with DNA repair activity or with XPC and DDB2 levels, but p63 levels were deficient in cell lines with reduced global repair. Repair-proficient SCC25 cells depleted of p63 lost XPC expression, early global DNA repair activity and UV resistance. These results demonstrate that some SCC cell lines are deficient in global nucleotide excision repair and support a role for p63 as a regulator of nucleotide excision repair in SCCs.

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Section: Introductionmentioning

confidence: 99%

Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells

Dong

Ona

Scandurra

et al. 2016

Photochem & Photobiology

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“…NER in eukaryotes has been the subject of extensive reviews, for example [3, 4], and human disorders caused by defective NER have been described [5-7]. The sequence of events in human GGR is the same as that in unicellular prokaryotes, but the process is more complicated and the number of proteins involved is much larger than in E. coli , as shown in Figure 1.…”

Section: Global and Transcription-coupled Repair In Human Cellsmentioning

confidence: 99%

Nucleotide excision repair in humans

2015

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The demonstration of DNA damage excision and repair replication by Setlow, Howard-Flanders, Hanawalt and their colleagues in the early 1960s, constituted the discovery of the ubiquitous pathway of nucleotide excision repair (NER). The serial steps in NER are similar in organisms from unicellular bacteria to complex mammals and plants, and involve recognition of lesions, adducts or structures that disrupt the DNA double helix, removal of a short oligonucleotide containing the offending lesion, synthesis of a repair patch copying the opposite undamaged strand, and ligation, to restore the DNA to its original form. The transcription-coupled repair (TCR) subpathway of NER, discovered nearly two decades later, is dedicated to the removal of lesions from the template DNA strands of actively transcribed genes. In this review I will outline the essential factors and complexes involved in NER in humans, and will comment on additional factors and metabolic processes that affect the efficiency of this important process.

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“…Cerebro-oculo-facio-skeletal syndrome (COFS) is considered to be a severe form of CS, with symptoms appearing at birth ( Suzumura and Arisaka, 2010 ), and XPF-ERCC1 progeroid (XFE) syndrome is associated with renal and liver abnormalities ( Niedernhofer et al , 2006 ). However, UV-sensitive syndrome (UVSS) has been described as a mild genetic disorder leading to skin photosensitivity ( Spivak, 2005 ; Oh and Spivak, 2010 ). Curiously, all these syndromes show skin photosensitivity and defects impairing NER, but among their clinical features, there has been no report of increased cancer frequency.…”

Section: Other Ner-defective Genetic Disordersmentioning

confidence: 99%

“…The increased sensitivity to UV-light is also observed in cells from XP, CS, TTD, or UVSS patients. Thus, the defective removal of UV photoproducts likely results in this photosensitivity ( Lehmann, 2003 ; Oh and Spivak, 2010 ). However, although these syndromes reflect defects on the same DNA processing pathway, apart from photosensitivity, they are clinically highly heterogeneous, including increased carcinogenesis, and more severe clinical features, such as abnormal development, neurodegeneration and premature aging.…”

Section: Dna Damage and Repair Vs Cancermentioning

confidence: 99%

DNA repair diseases: what do they tell us about cancer and aging?

2014

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The discovery of DNA repair defects in human syndromes, initially in xeroderma pigmentosum (XP) but later in many others, led to striking observations on the association of molecular defects and patients’ clinical phenotypes. For example, patients with syndromes resulting from defective nucleotide excision repair (NER) or translesion synthesis (TLS) present high levels of skin cancer in areas exposed to sunlight. However, some defects in NER also lead to more severe symptoms, such as developmental and neurological impairment and signs of premature aging. Skin cancer in XP patients is clearly associated with increased mutagenesis and genomic instability, reflecting the defective repair of DNA lesions. By analogy, more severe symptoms observed in NER-defective patients have also been associated with defective repair, likely involving cell death after transcription blockage of damaged templates. Endogenously induced DNA lesions, particularly through oxidative stress, have been identified as responsible for these severe pathologies. However, this association is not that clear and alternative explanations have been proposed. Despite high levels of exposure to intense sunlight, patients from tropical countries receive little attention or care, which likely also reflects the lack of understanding of how DNA damage causes cancer and premature aging.

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Hereditary Photodermatoses

Cited by 5 publications

References 44 publications

Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells

Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells

Nucleotide excision repair in humans

DNA repair diseases: what do they tell us about cancer and aging?

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