Typical xeroderma pigmentosum complementation group A fibroblasts have detectable ultraviolet light-induced unscheduled DNA synthesis

Petinga, Robert A.; Andrews, Alan D.; Tarone, Robert E.; Robbins, Jay H.

doi:10.1016/0005-2787(77)90033-8

Cited by 34 publications

(9 citation statements)

References 16 publications

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“…The detection of UDS in a fraction of the UV-irradiated nondividing XP1 2BE cells suggests that some excision repair occurs in this strain. This is consistent with the results of others using proliferating populations (40). Although no loss of dimers was observed in irradiated XPl 2BE populations (Fig.…”

Section: Sedimentation In Alkaline Sucrosesupporting

confidence: 93%

“…No variations from that observed for control populations in the DNA alkaline sucrose sedimentation profiles were observed for any UV-irradiated population. Results of a typical experiment for arrested WS-1 populations using 40 these experiments before 48 h after UV. We can detect no loss of acid-precipitable DNA in irradiated populations through a 48-h postirradiation period ( Fig.…”

Section: Sedimentation In Alkaline Sucrosementioning

confidence: 99%

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Repair of radiation-induced DNA damage in nondividing populations of human diploid fibroblasts

Kantor¹,

Petty²,

Warner³

et al. 1980

Biophysical Journal

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The occurrence of DNA repair in UV- (254 nm) and X-irradiated normal human diploid fibroblasts maintained in a quiescent, nondividing state using low serum (0.5%) medium was ascertained. Techniques that detect different steps of the excision repair process were used so that the extent of completion of repair at single sites could be determined. These included measuring the disappearance of pyrimidine dimers by chromatography, detecting repair synthesis by density-gradient and autoradiographic methods and detecting the rejoining of repaired regions and repair of x-ray-induced single-strand DNA breaks using alkaline sucrose gradients. Results show that dimer excision occurs and the subsequent steps of repair synthesis and ligation are completed. About 50% of the dimers formed by exposure to 20 J/m2 is excised in the initial 24-h post-UV period. DNA repair (unscheduled DNA synthesis) can be detected through a 5-d post-UV period. The fraction of damaged sites eventually repaired is not known. X-ray-induced single-strand DNA breaks are repaired rapidly.

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Section: Sedimentation In Alkaline Sucrosesupporting

confidence: 93%

Section: Sedimentation In Alkaline Sucrosementioning

confidence: 99%

Repair of radiation-induced DNA damage in nondividing populations of human diploid fibroblasts

Kantor¹,

Petty²,

Warner³

et al. 1980

Biophysical Journal

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“…Compound heterozygous mutations were detected in the XPA DNA repair gene (Table 1) with G>T intron 3 splice acceptor, and G>C splice donor of exon 4 [37,38]. The post-UV DNA repair rate (unscheduled DNA synthesis (UDS)) of the cultured skin fibroblasts was about 1% of normal [4,35,39,40]. Post-UV survival of cultured skin fibroblasts was markedly reduced [41].…”

Section: Resultsmentioning

confidence: 99%

The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

Lai

Liu

Alimchandani

et al. 2013

acta neuropathol commun

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BackgroundTo investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D.ResultsThe XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient.ConclusionsThese clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients.

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“…If populations of nucleotide excision repair-proficient cells are irradiated with UV light (wavelength, 254 nm) 17 h after release from confluence, the frequency of 6-thioguanine (TG)-resistant (TG') mutants (resulting from loss of function of the gene coding for hypoxanthine [guanine] phosphoribosyltransferase [HPRT]) is significantly higher than in cells irradiated in early G1 phase (9). This difference in frequency cannot be attributed to differences in the physical state of the DNA, since no such difference in mutation frequency is found when diploid xeroderma pigmentosum cells (XP12BE, complementation group A), which are virtually devoid of nucleotide excision repair (18), are irradiated in early S phase or in early G1 phase (9). These data suggest that S-phase replication is centrally involved in the conversion of potentially mutagenic DNA damage into mutations (fixation) and that excision repair prior to the onset of S phase decreases the frequency of mutants by eliminating such lesions.…”

mentioning

confidence: 99%

Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells.

McGregor¹,

Chen²,

Лукаш³

et al. 1991

Mol. Cell. Biol.

140

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To study the effect of nucleotide excision repair on the spectrum of mutations induced in diploid human fibroblasts by UV light (wavelength, 254 nm), we synchronized repair-proficient cells and irradiated them when the HPRT gene was about to be replicated (early S phase) so that there would be no time for repair in that gene before replication, or in G, phase 6 h prior to S, and determined the kinds and location of mutations in that gene. As a control, we also compared the spectra of mutations induced in synchronized populations of xeroderma pigmentosum cells (XP12BE cells, which [HPRT]) is significantly higher than in cells irradiated in early G1 phase (9). This difference in frequency cannot be attributed to differences in the physical state of the DNA, since no such difference in mutation frequency is found when diploid xeroderma pigmentosum cells (XP12BE, complementation group A), which are virtually devoid of nucleotide excision repair (18), are irradiated in early S phase or in early G1 phase (9). These data suggest that S-phase replication is centrally involved in the conversion of potentially mutagenic DNA damage into mutations (fixation) and that excision repair prior to the onset of S phase decreases the frequency of mutants by eliminating such lesions.Of the two major classes of potentially mutagenic UV photoproducts, i.e., cyclobutane pyrimidine dimers (Py-Py dimers) and 6-4 pyrimidine-pyrimidone (6-4 Py-Py) lesions, the latter have been shown to be removed from human genomic DNA more rapidly than the former (15). It has also been shown that Py-Py dimers are excised more rapidly from an actively transcribed gene of human cells, the dihydrofolate reductase gene (DHFR), than from bulk DNA (1, 12). Moreover, Mellon et al. (14) demonstrated that there is a strand bias in the rate of removal of Py-Py dimers from the * Corresponding author. DHFR gene in human cells. The majority of such lesions are removed within 24 h, but dimers in the transcribed strand are excised much faster than those in the nontranscribed strand. Information on strand-specific excision repair of UV-induced damage from the HPRT gene of human cells is not yet available, but if such repair occurs, HPRT mutations induced by UV in excision repair-proficient human cells irradiated at the onset of S phase should arise from 6-4 Py-Py lesions and Py-Py dimers located in either strand of DNA. In contrast, the lesions responsible for the mutations induced in such cells allowed 6 h for repair before the onset of S phase should arise mainly from Py-Py dimers, and these should be located primarily in the nontranscribed strand. This switch in strands should not occur in XP12BE cells.There are no published data on the kinds and locations (i.e., the spectrum) of UV-induced mutations in an endogenous gene of human cells, nor are there data showing whether excision repair in such cells alters the spectrum. This study was designed to examine the spectrum of mutations induced by UV in the HPRT gene of diploid human cells and to determine, at the DNA ...

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Typical xeroderma pigmentosum complementation group A fibroblasts have detectable ultraviolet light-induced unscheduled DNA synthesis

Cited by 34 publications

References 16 publications

Repair of radiation-induced DNA damage in nondividing populations of human diploid fibroblasts

Repair of radiation-induced DNA damage in nondividing populations of human diploid fibroblasts

The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells.

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