Three-Dimensional Visualization of Ultraviolet-Induced DNA Damage and Its Repair in Human Cell Nuclei

Nakagawa, Akemi; Kobayashi, Nobuhiko; Muramatsu, Tsutomu; Yamashina, Yukio; Shirai, Toshihiko; Hashimoto, Mitsumasa; Ikenaga, Mituo; Mori, Toshio

doi:10.1046/j.1523-1747.1998.00100.x

Cited by 76 publications

(45 citation statements)

References 37 publications

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“…This procedure was described previously. [46][47] Briefly, 2 x 10 4 cells seeded/well in 24 well culture plates were infected with Ad-LacZ or Ad-AS-BRCA1 at 40 MOI for 24 hrs, then irradiated with 20 J/m 2 UVC. Cells were fixed immediately, at 6 hrs, 24 hrs, and 48 hrs after irradiation with cold (4°C) methanol-acetic acid (3:1) for one hour.…”

Section: Methodsmentioning

confidence: 99%

BRCA1 Transcriptionally Regulates Damaged DNA Binding Protein (DDB2) In the DNA Repair Response Following UV-Irradiation

Takimoto¹,

MacLachlan²,

Dicker³

et al. 2002

Cancer Biology & Therapy

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© 2 0 0 2 L a n d e s B i o s c i e n c e . N o t f o r d i s t r i b u t i o n .[Cancer Biology & ABSTRACTThe p53 and BRCA1 tumor suppressors are involved in repair processes and may cooperate to transactivate certain genes, including p21WAF1/CIP1 and GADD45. We find that the Xeroderma Pigmentosum Complementation group E (XPE) mutated Damaged-DNA binding protein p48 (DDB2) is upregulated by BRCA1 in a p53-dependent manner following UVC, Adriamycin, or Cisplatin exposure. BRCA1 enhances p53 binding to the DDB2 promoter in vivo as well as p53-dependent transactivation of DDB2 promoterreporter constructs through a classical p53 DNA responsive element. Antisense abrogation of BRCA1 expression abrogates upregulation of DDB2 after UVC or cisplatin exposure. Using a host cell reactivation assay, DNA repair activity is more significantly restored by introduction of BRCA1 into wt as compared to DDB2-deficient cells. Furthermore disappearance of the photoproducts cyclobutane pyrimidine dimer (CPD) and 6-4 photoproduct (6-4PP) was delayed by antisense abrogation of BRCA1 expression in UV-exposed human cells. Thus the DNA repair function of BRCA1 may be attributed in part to p53-dependent transcriptional induction of DDB2. Loss of BRCA1-dependent DDB2 repair function may contribute to cancer susceptibility and cellular sensitivity to DNA damage.

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Section: Methodsmentioning

confidence: 99%

BRCA1 Transcriptionally Regulates Damaged DNA Binding Protein (DDB2) In the DNA Repair Response Following UV-Irradiation

Takimoto¹,

MacLachlan²,

Dicker³

et al. 2002

Cancer Biology & Therapy

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“…This procedure was described previously (26,27). Briefly, 5 ϫ 10 6 cells were seeded on 15-cm culture dishes and irradiated with 0, 15, 22.5, and 30 J͞m 2 UVC as described above.…”

Section: Methodsmentioning

confidence: 99%

“…We used an ELISA assay and specific mAbs (26,27) to further assess the repair kinetics of CPD and 6-4PP in the two transfectants. As shown in Fig.…”

Section: The Partially and Fully Corrected Xpc Clones Regained Differmentioning

confidence: 99%

“…We constructed a partially corrected (XP4PA-SE1) and a fully corrected (XP4PA-SE2) cell line by stable transfection of an XPC cell line, XP4PA-SV-EB, with the plasmid pXPC3, which contains XPC cDNA. The ability to repair UV-induced DNA damage was assessed by UV cell survival (24), a plasmid host cell reactivation assay (25), and directly with a photoproduct removal ELISA and specific mAbs (26,27). Increased, but still subnormal, XPC protein levels led to a partial functional correction in XP4PA-SE1 by reconstituting cyclobutane pyrimidine dimer (CPD) but not 6-4 photoproduct (6-4PP) repair in the cells' global genome.…”

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The xeroderma pigmentosum group C gene leads to selective repair of cyclobutane pyrimidine dimers rather than 6-4 photoproducts

Emmert

Kobayashi

Khan

et al. 2000

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

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, whereas the fully corrected XP4PA-SE2 cells regained normal CPD and 6-4PP repair capacities. We also exposed pRSVcat plasmid to UVC (to induce CPD and 6-4PP), to UVC ؉ photolyase (to leave only 6-4PP on the plasmid), or to UVB ؉ acetophenone (to induce only CPD). Host cell reactivation of UVB ؉ acetophenone-, but not of UVC ؉ photolyase-treated plasmids was normal in XP4PA-SE1 cells. Thus, increasing XPC gene expression leads to selective repair of CPD in the global genome. Undetectable XPC protein is associated with no repair of CPD or 6-4PP, detectable but subnormal XPC protein levels reconstitute CPD but not 6-4PP repair, and normal XPC protein levels fully reconstitute both CPD and 6-4PP repair.

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“…Despite these detrimental effects of UVR, it is required to produce vitamin D 3 in skin cells. Vitamin D 3 is produced in the skin following exposure of its precursor, 7-dehydrocholesterol, to UVR (6). Following 2 successive hydroxylation reactions, the biologically active steroid hormone 1a,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] is formed.…”

Section: Introductionmentioning

confidence: 99%

1α,25(OH)2-Vitamin D and a Nongenomic Vitamin D Analogue Inhibit Ultraviolet Radiation–Induced Skin Carcinogenesis

Dixon

Norman

Sequeira

et al. 2011

Cancer Prevention Research

106

153

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Exposure to ultraviolet radiation (UVR) can lead to a range of deleterious responses in the skin. An important form of damage is the DNA photolesion cyclobutane pyrimidine dimer (CPD). CPDs can be highly mutagenic if not repaired prior to cell division and can lead to UV-induced immunosuppression, making them potentially carcinogenic. UVR exposure also produces vitamin D, a prehormone. Different shapes of the steroid hormone 1a,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] can produce biological responses through binding either to its cognate nuclear receptor (VDR) to regulate gene transcription or to the VDR associated with plasma membrane caveolae to produce, via signal transduction, nongenomic physiologic responses. Here, we show that both 1,25(OH) 2 D 3 and 1a,25(OH) 2 -lumisterol (JN), a conformationally restricted analogue that can generate only nongenomic responses, are effective inhibitors of UV damage in an immunocompetent mouse (Skh:hr1) model susceptible to UV-induced tumors. Both 1,25(OH) 2 D 3 and JN significantly reduced UVR-induced CPD, apoptotic sunburn cells, and immunosuppression. Furthermore, these compounds inhibited skin tumor development, both papillomas and squamous cell carcinomas, in these mice. The observed reduction of these UV-induced effects by 1,25 (OH) 2 D 3 and JN suggests a role for these compounds in prevention against skin carcinogenesis. To the best of our knowledge, this is the first comprehensive report of an in vivo long-term biological response generated by chronic dosing with a nongenomic-selective vitamin D steroid.

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Three-Dimensional Visualization of Ultraviolet-Induced DNA Damage and Its Repair in Human Cell Nuclei

Cited by 76 publications

References 37 publications

BRCA1 Transcriptionally Regulates Damaged DNA Binding Protein (DDB2) In the DNA Repair Response Following UV-Irradiation

BRCA1 Transcriptionally Regulates Damaged DNA Binding Protein (DDB2) In the DNA Repair Response Following UV-Irradiation

The xeroderma pigmentosum group C gene leads to selective repair of cyclobutane pyrimidine dimers rather than 6-4 photoproducts

1α,25(OH)2-Vitamin D and a Nongenomic Vitamin D Analogue Inhibit Ultraviolet Radiation–Induced Skin Carcinogenesis

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