Tendency to high levels of UVR-induced unscheduled DNA synthesis in bloom syndrome

Giannelli, F.; Pawsey, S.A.; Botcherby, P. K.

doi:10.1016/0027-5107(81)90037-3

Cited by 15 publications

(6 citation statements)

References 21 publications

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Section: Introductionmentioning

confidence: 99%

“…A slight decrease in the rate of DNA fork displacement during replication has also been observed for BS cells (11,12). Moreover, such cells show slightly increased sensitivity to ultraviolet and near-ultraviolet light accompanied by altered unscheduled DNA synthesis and increased chain breakage compared to control cells, indicative of an abnormality in a postincision step of DNA excision-repair (13,14).We have shown previously (15) that the level of activity of the major DNA ligase in proliferating human cells, ligase I, is reduced in the BS-derived lymphoblastoid cell line GM3403.Furthermore, the ligase I in these cells is anomalously heatlabile, indicating a mutation in the structural gene for DNA ligase I in this line (15). Preliminary observations on altered aggregation properties of ligase I from other BS cell lines have also been made (15,16).…”

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confidence: 99%

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Structural alterations of DNA ligase I in Bloom syndrome.

Willis¹,

Weksberg²,

Tomlinson³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Cell lines derived from seven patients with Bloom syndrome all contain a DNA ligase I with unusual properties. Six lines were shown to have a reduced level of this enzyme activity and the residual enzyme was anomalously heat-labile. The seventh line contained a dimeric rather than monomeric form of ligase I. Several cell lines representative of other inherited human syndromes have apparently normal DNA ligases. The data indicate that Bloom syndrome is due to a defect in the structure of DNA ligase I caused by a "leaky" point mutation occurring at one of at least two alternative sites.The rare syndrome first described by Bloom in 1954 as a "congenital telangiectatic erythema resembling lupus erythematosus in dwarfs" (1) is associated with a greatly increased incidence of cancer. Thus, in a recent survey of this recessively inherited disease, 28 malignant neoplasms of several different types were detected in 103 young patients (2). Most cases of Bloom syndrome (BS) have been found among Ashkenazim, and it has been estimated that about 1% of this population represent BS heterozygotes (3). However, the disorder has also been reported in non-Jewish individuals, including American blacks (4) and Japanese (5).Cells from BS patients exhibit frequent chromosome rearrangements [in particular, symmetrical quadriradials indicative of exchanges between homologous chromatids at homologous sites (6, 7)], and a 15-to 20-fold increased level of spontaneous sister-chromatid exchange (SCE) is regarded as a hallmark of the disease (8). In addition, BS cells show a 5-to 10-fold elevated spontaneous mutation rate (9). Ten years ago, Giannelli et al. (10) found that replicative intermediates of DNA exhibit delayed maturation into a very high-molecular weight form in BS cells and suggested that the fundamental defect involves a step in DNA replication. A slight decrease in the rate of DNA fork displacement during replication has also been observed for BS cells (11,12). Moreover, such cells show slightly increased sensitivity to ultraviolet and near-ultraviolet light accompanied by altered unscheduled DNA synthesis and increased chain breakage compared to control cells, indicative of an abnormality in a postincision step of DNA excision-repair (13,14).We have shown previously (15) that the level of activity of the major DNA ligase in proliferating human cells, ligase I, is reduced in the BS-derived lymphoblastoid cell line GM3403.Furthermore, the ligase I in these cells is anomalously heatlabile, indicating a mutation in the structural gene for DNA ligase I in this line (15). Preliminary observations on altered aggregation properties of ligase I from other BS cell lines have also been made (15,16). In the present work, we extend our molecular analysis to six additional BS cell lines and show that two clearly distinguishable types of ligase I defects occur in patients with this clinical syndrome. MATERIALS AND METHODSCell Lines and Cell Culture. Five BS cell lines were derived from different Ashkenazi BS patients. The simian viru...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Structural alterations of DNA ligase I in Bloom syndrome.

Willis¹,

Weksberg²,

Tomlinson³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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“…UV radiation modulates the rate of spontaneous unscheduled DNA repair observed in BS and LE cell lines, suggesting that the mechanism of DNA injury may involve a similar biomolecular pathway. 25 Viewed simply, BS and LE are diseases of keratinocyte photoinjury. Regardless of the specific mechanism, damaged keratinocytes may unmask previously hidden epitopes and promote a ''loss of tolerance'' effect.…”

Section: Discussionmentioning

confidence: 99%

“…The authors proposed that a greater number of damaged DNA sites were repaired and, therefore, DNA from patients with BS exhibits a greater vulnerability to UVR than does DNA from normal controls. 25 Such findings indicate that DNA injury in photogenodermatoses varies according to the unique spectrum of radiant energy and specific mutation in the DNA reparative process.…”

Section: Molecular Geneticsmentioning

confidence: 97%

Lupus-Like Histopathology in Bloom Syndrome: Reexamining the Clinical and Histologic Implications of Photosensitivity

McGowan

Maize

Cook

2009

The American Journal of Dermatopathology

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“…13 A histopatologia das lesões encontradas nestes pacientes são descritas como lesões lupus-like, como as vistas no relato de caso de McGowan e nas descrições iniciais de Giannelli. 13,14 A avaliação citogenética, parte do diagnóstico proposto pelo Bloom's Syndrome Registry, pode ser realizada através da técnica G bands ou pelo método Sister Chromatid Exchange (SCE), neste encontramos uma enorme quantidade de troca de cromátides irmãs no estudo de culturas de linfócitos. 7,8 O tratamento da síndrome consiste em suporte clínico, uso de fotoprotetores, acompanhamento regular para flagrar surgimento de neoplasias e para cuidados com processos infecciosos de repetição.…”

Section: Discussionunclassified

Síndrome de Bloom: relato de dois casos

Frota¹,

Matos²,

Carneiro³

et al. 2015

Rev. Med. UFC

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RESUMOSíndrome de Bloom é uma doença autossômica recessiva caracterizada por eritema telangiectásico em face, fotossensibilidade e retardo de crescimento pré e pós-natal. A mutação do gene BLM, traz uma instabilidade cromossômica importante, responsável pelas manifestações da síndrome e pela maior susceptibilidade a neoplasias. Há um registro mundial de pacientes com um total de 255 casos, sendo 16 do Brasil. Diante da raridade da síndrome, apresentamos o caso de duas irmãs, filhas de pais consanguíneos, ambas com baixa estatura, apresentando máculas eritematosas com telangiectasias em nariz e região perioral, micrognatismo, dolicocefalia, hipoplasia malar, face triangular, nariz proeminente, máculas hipocrômicas e manchas café com leite em tronco e membros inferiores. O diagnóstico é clínico e pode ser confirmado por citogenética. Os portadores apresentam fenótipo típico com telangiectasias em áreas fotoexpostas. Ainda não há tratamento específico, porém, deve-se oferecer suporte clínico e melhoria da qualidade de vida e diminuição de estigmas.Palavras chave: Síndrome de Bloom. Eritema telangiectásico congênito. Eritema. Telangiectasia. ABSTRACTBloom's syndrome is an autosomal recessive disorder characterized by telangiectatic erythema in the face, photosensitivity and growth retardation. BLM gene mutation brings an important chromosomal instability, responsible for the manifestations and the higher susceptibility to cancer. A global registry of patients comprises a total of 255 cases, 16 from Brazil. Due to the rarity of the syndrome, we present the case of two sisters, daughters of consanguineous parents, both with short stature and erythematous macules with telangiectasias in the nose and perioral region, micrognathia, dolichocephaly, malar hypoplasia, triangular face, prominent nose, hypochromic macules and café au lait spots on the trunk and lower limbs. The diagnosis is clinical and can be confirmed by cytogenetics. The patients have typical phenotype with telangiectasias on sun-exposed areas. There is still no specific treatment, however, supportive care should be offered, associated with an improvement of the quality of life and reduction of stigma.

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Tendency to high levels of UVR-induced unscheduled DNA synthesis in bloom syndrome

Cited by 15 publications

References 21 publications

Structural alterations of DNA ligase I in Bloom syndrome.

Structural alterations of DNA ligase I in Bloom syndrome.

Lupus-Like Histopathology in Bloom Syndrome: Reexamining the Clinical and Histologic Implications of Photosensitivity

Síndrome de Bloom: relato de dois casos

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