DNA Repair in Bacteria and Mammalian Cells

Hanawalt, Philip C.; Cooper, Priscilla K.; Ganesan, Ann K.; Smith, Charles A.

doi:10.1146/annurev.bi.48.070179.004031

Cited by 833 publications

(218 citation statements)

References 2 publications

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“…UV-induced lesions are removed from the genome by the efficient NER pathway. In contrast, it is accepted that NER activity is considerably lower in mouse fibroblasts than in human cells (21). Quantitative analysis of UV-B (500-J/m 2 )-induced DNA lesions in mouse skin using damage-specific antibodies has revealed differences in the repair efficiencies of CPDs and (6-4)PPs in epidermis and dermis (51).…”

Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorsmentioning

confidence: 99%

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Ohkumo

Kondo

Yokoi

et al. 2006

Molecular and Cellular Biology

107

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DNA polymerase(Pol ) is the product of the Polh gene, which is responsible for the group variant of xeroderma pigmentosum, a rare inherited recessive disease which is characterized by susceptibility to sunlightinduced skin cancer. We recently reported in a study of Polh mutant mice that Pol is involved in the somatic hypermutation of immunoglobulin genes, but the cancer predisposition of Polh ؊/؊ mice has not been examined until very recently. Another translesion synthesis polymerase, Pol , a Pol paralog encoded by the Poli gene, is naturally deficient in the 129 mouse strain, and the function of Pol is enigmatic. Here, we generated Polh Poli doubledeficient mice and compared the tumor susceptibility of them with Polh-or Poli-deficient animals under the same genetic background. While Pol deficiency does not influence the UV sensitivity of mouse fibroblasts irrespective of Polh genotype, Polh Poli double-deficient mice show slightly earlier onset of skin tumor formation. Intriguingly, histological diagnosis after chronic treatment with UV light reveals that Pol deficiency leads to the formation of mesenchymal tumors, such as sarcomas, that are not observed in Polh ؊/؊ mice. These results suggest the involvement of the Pol and Pol proteins in UV-induced skin carcinogenesis.

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Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorsmentioning

confidence: 99%

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Ohkumo

Kondo

Yokoi

et al. 2006

Molecular and Cellular Biology

107

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“…This study demonstrated that skin fibroblast strains derived from five members of a polyposis/sarcoma family (Figure 1; Table I) exhibit abnormal resistance to reproductive inactivation by 4NQO (Table II), a partially UV-mimetic and radiomimetic carcinogen (Regan & Setlow, 1974;Hanawalt et al, 1979;Smith & Paterson, 1980). This unusual cytotoxic response for noncancerous cell types correlated with the introduction of an abnormally low amount of genomic DNA damage on exposure to a given concentration of 4NQO, as a result of decreased accumulation of the chemical in resistant compared to normal fibroblasts (Table III).…”

Section: Discussionmentioning

confidence: 95%

“…4HAQO is in turn esterified to acyl-4HAQO, an ultimate carcinogen that reacts at the N2 and the C8 positions of guanosine and at the N6 position of adenosine (Tada & Tada, 1975;Galiegue-Zouitina et al, 1985). In repair-competent human cells, 4NQO-induced DNA lesions are operated on by both the nucleotide and base modes of excision repair (Regan & Setlow, 1974;Hanawalt et al, 1979).…”

mentioning

confidence: 99%

Hyperresistance to 4-nitroquinoline 1-oxide cytotoxicity and reduced DNA damage formation in dermal fibroblast strains derived from five members of a cancer-prone family

Mirzayans¹,

Sabour²,

Rauth³

et al. 1993

Br J Cancer

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Summary Dermal fibroblasts cultured from members of a family presenting multiple polyps and sarcomas were compared with fibroblast strains from unrelated healthy donors for sensitivity to killing by four genotoxic agents. Cells from the sister of the male proband (strain 3437T), mother (strain 3703T), two of his paternal aunts (3701T and 3704T) and one paternal uncle (3702T) displayed marked resistance (1.8 to 4.3 times greater than the normal mean) to 4-nitroquinoline 1-oxide (4NQO), a procarcinogen whose DNAdamaging properties encompass those of both far (254 nm) ultraviolet (UV) light and ionising radiation. These same 4NQO-resistant cells, however, responded normally to reproductive inactivation by UV light, 'Co radiation or the alkylating agent methylnitrosourea, signifying that the abnormal resistance of these cells to 4NQO is not associated with aberrant DNA metabolism. In keeping with this conclusion, exposure to a given dose of 4NQO produced decreased amounts of DNA damage and stimulated lower levels of repair DNA synthesis in all five 4NQO-resistant strains than in normal controls. Moreover, exogenous radiolabelled 4NQO accumulated to a lesser extent in the 4NQO-resistant than in the normal fibroblasts. Cell sonicates of strains 3437T, 3701T and 3702T exhibited reduced capacities (40-60% of normal) to catalise the conversion of 4NQO to the proximate carcinogen 4-hydroxyaminoquinoline 1-oxide. However, the 4NQO-resistant strains 3703T and 3704T carried out 4NQO bioreduction at normal rates. Our data therefore indicate that enhanced resistance to 4NQO cytotoxicity in 3437T, 3701T and 3702T is a consequence of anomalies in both intracellular accumulation and enzymatic reduction of 4NQO, whereas 4NQO resistance in 3703T and 3704T appears to result solely from reduced intracellular drug accumulation.

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“…Incision is the first step in excision repair of ultraviolet-damaged DNA, and is controlled by at least three genes, uvrA, uvrB and uvrC, in Escherichia coli (1)(2)(3). The products of these genes are components of an enzyme that induces strand breaks at both sides of a pyrimidine dimer, thereby releasing a damaged portion of nucleotides from the DNA (4,5).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of the UvrABC enzyme-catalyzed repair reactions by the UvrD protein (DNA helicase II)

Kumura¹,

Sekiguchi²,

Stemum

et al. 1985

Nucl Acids Res

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DNA Repair in Bacteria and Mammalian Cells

Cited by 833 publications

References 2 publications

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Hyperresistance to 4-nitroquinoline 1-oxide cytotoxicity and reduced DNA damage formation in dermal fibroblast strains derived from five members of a cancer-prone family

Stimulation of the UvrABC enzyme-catalyzed repair reactions by the UvrD protein (DNA helicase II)

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