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S. Kirk-Bell

Bio: S. Kirk-Bell is an academic researcher from University of Sussex. The author has contributed to research in topics: Nucleotide excision repair & Xeroderma pigmentosum. The author has an hindex of 2, co-authored 4 publications receiving 812 citations.

Papers
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Journal ArticleDOI
TL;DR: Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.
Abstract: Cells cultured from most patients suffering from the sunlight-sensitive hereditary disorder xeroderma pigmentosum are defective in the ability to excise ultraviolet light (UV)-induced pyrimidine dimers from their DNA. There is, however, one class of these patients whose cells are completely normal in this excision repair process. We have found that these cells have an abnormality in the manner in which DNA is synthesized after UV-irradiation. The time taken to convert initially low-molecular-weight DNA synthesized in UV-irradiated cells into high-molecular-weight DNA similar in size to that in untreated cells is much greater in these variants than in normal cells. Furthermore, this slow conversion of low to high-molecular-weight newly synthesized DNA is drastically inhibited by caffeine, which has no effect in normal cells. Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.

616 citations

Journal Article
TL;DR: The defect in postreplication repair previously found in XP variants (excision-proficient XP's) has now been observed in a total of five XP variants and a less severe defect has been found in excision-defective XP's in Complementation Groups A, B, C, and D.
Abstract: Postreplication repair of DNA damage after ultraviolet light irradiation has been examined in a wide variety of human fibroblast strains. The donors were patients with xeroderma pigmentosum (XP) of different complementation groups or other hereditary disorders with indications of radiosensitivity, or with light sensitivity or multiple cancers. The defect in postreplication repair previously found in XP variants (excision-proficient XP's) has now been observed in a total of five XP variants and a less severe defect in postreplication repair has been found in excision-defective XP's in Complementation Groups A, B, C, and D. Complementation Group E and all other cell strains studied showed a response that was not significantly different from that of cells from normal donors. Excision repair was also measured in some of these cell strains and was found to be defective only in XP cells. Ultraviolet cell survival characteristics have been obtained for may of the cell strains. The most sensitive were cells from the excision-deficient XP's and from a sun-sensitive child (11961); the latter had no measurable defect in either excision or postreplication repair. The rest of the survival curves lay in a band limited by normal cell strains on the one hand and the slightly more sensitive excision-proficient XP variant XP30RO. Only in the case of the variants XP30RO and XP7TA were we able to demonstrate any influence of caffeine on cell survival.

199 citations

Book ChapterDOI
01 Jan 1977
TL;DR: Postreplication repair is defective in fibroblasts from all the xeroderma pigmentosum complementation groups with the exception of group E, the defect being most pronounced in the excision-proficient XP variants.
Abstract: Postreplication repair is defective in fibroblasts from all the xeroderma pigmentosum (XP) complementation groups with the exception of group E, the defect being most pronounced in the excision-proficient XP variants. It is normal in cells from patients with a variety of other disorders. During postreplication repair pyrimidine dimer sites become associated with daughter strands in both normal and XP cells.

2 citations

01 Jan 2016
TL;DR: It is found that cells cultured from most patients suffer from the sunlight-sensitive hereditary disorder xero- derma pigmentosum have an abnormal- ity in the manner in which DNA is synthesized after UV- irradiation.
Abstract: Cells cultured from most patients suffer- ing from the sunlight-sensitive hereditary disorder xero- derma pigmentosum are defective in the ability to excise ultraviolet light (UV)-induced pyrimidine dimers from their DNA. There is, however, one class of these patients whose cells are completely normal in this excision repair process. We have found that these cells have an abnormal- ity in the manner in which DNA is synthesized after UV- irradiation. The time taken to convert initially low- molecular-weight DNA synthesized in UV-irradiated cells into high-molecular-weight DNA similar in size to that in untreated cells is much greater in these variants than in normal cells. Furthermore, this slow conversion of low to high-molecular-weight newly synthesized DNA is dras- tically inhibited by caffeine, which has no effect in normal cells. Two cell lines from classes of xeroderma pigmento- sunm that are defective in excision-repair show inter- mediate effects, with regard to both the time taken to

Cited by
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Journal ArticleDOI
03 Dec 1999-Science
TL;DR: In some cases, DNA damage is not repaired but is instead bypassed by specialized DNA polymerases, and the integrity of the genetic information is compromised.
Abstract: Faithful maintenance of the genome is crucial to the individual and to species. DNA damage arises from both endogenous sources such as water and oxygen and exogenous sources such as sunlight and tobacco smoke. In human cells, base alterations are generally removed by excision repair pathways that counteract the mutagenic effects of DNA lesions. This serves to maintain the integrity of the genetic information, although not all of the pathways are absolutely error-free. In some cases, DNA damage is not repaired but is instead bypassed by specialized DNA polymerases.

1,502 citations

Journal ArticleDOI
17 Jun 1999-Nature
TL;DR: Recombinant human DNA polymerase η corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA, indicating that DNA polymerases η could be the XPV gene product.
Abstract: Xeroderma pigmentosum variant (XP-V) is an inherited disorder which is associated with increased incidence of sunlight-induced skin cancers. Unlike other xeroderma pigmentosum cells (belonging to groups XP-A to XP-G), XP-V cells carry out normal nucleotide-excision repair processes but are defective in their replication of ultraviolet-damaged DNA. It has been suspected for some time that the XPV gene encodes a protein that is involved in trans-lesion DNA synthesis, but the gene product has never been isolated. Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts. Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase eta. This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. We found that all XP-V cells examined carry mutations in their DNA polymerase eta gene. Recombinant human DNA polymerase eta corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. Together, these results indicate that DNA polymerase eta could be the XPV gene product.

1,314 citations

Journal ArticleDOI
TL;DR: Quantitative frequencies of clinical abnormalities in xeroderma pigmentosum were estimated by abstracting published descriptions of 830 patients in 297 articles obtained from a survey of the medical literature from 1874 to 1982, finding scant information concerning the efficacy of any therapeutic regimen.
Abstract: • Quantitative frequencies of clinical abnormalities in xeroderma pigmentosum were estimated by abstracting published descriptions of 830 patients in 297 articles obtained from a survey of the medical literature from 1874 to 1982. The median patient age was 12 years with nearly equal numbers of male and female patients. Cutaneous symptoms (sun sensitivity or freckling) had a median age of onset of between 1 and 2 years. Forty-five percent of the patients described had basal cell carcinoma or squamous cell carcinoma of the skin. The median age of first nonmelanoma skin cancer among patients with xeroderma pigmentosum was 8 years, more than 50 years less than that among patients with skin cancer in the United States. Melanomas were reported in 5% of patients. Ninety-seven percent of the reported basal and squamous cell carcinomas and 65% of the melanomas in patients with xeroderma pigmentosum occurred on the face, head, or neck. Seventy percent probability of survival was attained at age 40 years, a 28-year reduction in comparison with the US general population. Ocular abnormalities were reported in 40% of the patients described and were restricted to tissues exposed to ultraviolet radiation (lid, conjunctiva, and cornea) and included ectropion, corneal opacity leading to blindness, and neoplasms. Neurologic abnormalities were found in 18% of the cases reported, consisting of progressive mental deterioration, hyporeflexia or areflexia, and progressive deafness in some patients in association with dwarfism and immature sexual development. There was scant information concerning the efficacy of any therapeutic regimen. (Arch Dermatol1987;123:241-250)

1,136 citations

Journal ArticleDOI
TL;DR: This review focuses on eukaryotic translesion synthesis (TLS) DNA polymerases, and the emphasis is on Saccharomyces cerevisiae and human Y- family polymerases (Pols) eta, iota, kappa, and Rev1, as well as on Polzeta, which is a member of the B-family polymerases.
Abstract: ▪ Abstract This review focuses on eukaryotic translesion synthesis (TLS) DNA polymerases, and the emphasis is on Saccharomyces cerevisiae and human Y-family polymerases (Pols) η, ι, κ, and Rev1, as well as on Polζ, which is a member of the B-family polymerases. The fidelity, mismatch extension ability, and lesion bypass efficiencies of these different polymerases are examined and evaluated in the context of their structures.One major conclusion is that, despite the overall similarity of basic structural features among the Y-family polymerases, there is a high degree of specificity in their lesion bypass properties. Some are able to bypass a particular DNA lesion, whereas others are efficient at only the insertion step or the extension step of lesion bypass. This functional divergence is related to the differences in their structures. Polζ is a highly specialized polymerase specifically adapted for extending primer termini opposite from a diverse array of DNA lesions, and depending upon the DNA lesion, it ...

989 citations

Journal ArticleDOI
TL;DR: In this paper, the authors present an Ionizing Radiation Sources and Biological Effects (IRBE) study, in which the sources and biological effects of ionizing radiation are investigated and compared.
Abstract: (1983). Ionizing Radiation: Sources and Biological Effects. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 43, No. 5, pp. 585-586.

769 citations