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1.
J Photochem Photobiol B ; 162: 625-632, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27487467

RESUMO

C-myb proto-oncogene is a potential therapeutic target for some human solid tumors and leukemias. A long cytosine-rich sequence, which locates the downstream of the transcription initiation site, is demonstrated to fold into an intramolecular i-motif DNA using electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy. Effects of factors, including the pH value, the number of C:C(+) dimers, the concentration of buffer, the molecular crowding condition, and the coexistence of the complementary DNA, on the formation and the structural stability of the i-motif DNA are systematically studied. We have demonstrated that the i-motif folding in the c-myb promoter could be accelerated upon synergistic physiological stimuli including intracellular molecular crowding and low pH values, as well as the large number of the i-motif C:C(+) dimers. Meanwhile, various inputs, such as acids/bases and metal ions, have exhibited their abilities in controlling the conformational switch of the c-myb GC-rich DNA. Acidic pH values and the presence of K(+) ions can induce the dissociation of the double helix. Our present strategy can greatly extend the potential usages of i-motif DNA molecules with specific sequences as conformational switch-controlled devices. Moreover, this work demonstrates the superiority of CD spectroscopy associated with ESI-MS as a rapid, more cost-effective and sensitive structural change responsive method in the research of DNA conformational switching.


Assuntos
Proteínas Proto-Oncogênicas c-myb/genética , Sequência de Bases , Dicroísmo Circular , Humanos , Concentração de Íons de Hidrogênio , Íons/química , Conformação de Ácido Nucleico , Potássio/química , Regiões Promotoras Genéticas , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-myb/química , Dímeros de Pirimidina/química , Espectrometria de Massas por Ionização por Electrospray
2.
J Invest Dermatol ; 134(11): 2806-2813, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24844860

RESUMO

Skin cancer is caused by solar UVR, which is also essential for vitamin D production. DNA damage (thymine dimers: T-T dimers) and vitamin D (25(OH)D) synthesis are both initiated by solar UVB. We aimed to investigate the simultaneous adverse and beneficial effects of solar UVB exposure in holidaymakers. Sun-seekers and skiers (n=71) were observed over 6 days through on-site monitoring, personal diary entries, and recording of personal UVB exposure doses with electronic dosimeters. Urine and blood samples were analyzed for T-T dimers and 25(OH)D, respectively. The volunteers had a statistically significant increase in vitamin D. There were strong associations between UVB exposure and post-holiday levels of T-T dimers and vitamin D, as well as between post-holiday T-T dimers and vitamin D. We conclude that UVB-induced vitamin D synthesis is associated with considerable DNA damage in the skin. These data, on two major health predictors, provide a basis for further field studies that may result in better understanding of the risks and benefits of "real life" solar exposure. However, vitamin D status can be improved more safely through the use of vitamin D dietary supplements.


Assuntos
Dano ao DNA , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Deficiência de Vitamina D/prevenção & controle , Deficiência de Vitamina D/terapia , Vitamina D/sangue , Adulto , Praias , Feminino , Férias e Feriados , Humanos , Masculino , Pessoa de Meia-Idade , Dímeros de Pirimidina/química , Esqui , Pele/efeitos da radiação , Neoplasias Cutâneas/etiologia , Fatores de Tempo
3.
Photochem Photobiol Sci ; 12(1): 95-103, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23192740

RESUMO

Long wavelength UVA1 (340-400 nm) is the main component of terrestrial UVR and is increasingly used in skin phototherapy. Its damage to critical biomolecules such as DNA has been widely attributed to its ability to generate reactive oxygen species (ROS) via other chromophores. However recent studies in vitro and in vivo have shown that UVA1 has a specific ability to generate cyclobutane pyrimidine dimers (CPD), especially thymine dimers (T<>T), and that this is probably due to direct absorption of UVR. The CPD has been implicated in many aspects of skin cancer. Measuring UVB-induced CPD in the epidermis and dermis in vivo shows that, as expected, the skin attenuates UVB. In contrast, our data show that this is not the case with UVA1: in fact there is more damage with increased skin depth. This suggests that the basal layer, which contains keratinocyte stem cells and melanocytes, is more vulnerable to the carcinogenic effects of UVA1 than would be predicted by mouse models. These data support the continuing trend for better UVA1 protection by sunscreens.


Assuntos
Pele/efeitos da radiação , Raios Ultravioleta , Animais , Dano ao DNA/efeitos da radiação , Eritema/etiologia , Humanos , Camundongos , Mutação , Dímeros de Pirimidina/química , Dímeros de Pirimidina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Pele/química , Pele/metabolismo , Neoplasias Cutâneas/etiologia
4.
Arch Dermatol Res ; 300(6): 331-4, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18401588

RESUMO

Exposure to ultraviolet B (UVB) irradiation is a major risk factor for the development of skin cancer. Therefore, it is important to identify agents that can offer protection against UVB-caused DNA damage. Photocarcinogenesis is caused largely by mutations at the sites of incorrectly repaired DNA photoproducts, of which the most common are the cyclobutane pyrimidine dimers (CPDs). In this study, a DNA damage model of UVB irradiation-induced fibroblasts was established. The immunocytochemical staining, immuno dot blotting and Western blotting were employed in the study. We demonstrated that pre-treatment of fibroblasts with Baicalin dose-dependently reduced the amount of UVB-generated CPDs. Compared with UVB irradiated cells, UVB-induced p53 accumulation was less pronounced in Baicalin-treated cells. Taken together, these results suggest that Baicalin prevent CPDs formation induced by UVB. Baicalin is therefore a promising protective substance against UVB radiation.


Assuntos
Dano ao DNA/efeitos da radiação , Fibroblastos/efeitos da radiação , Flavonoides/farmacologia , Dímeros de Pirimidina/efeitos da radiação , Células Cultivadas , Pré-Escolar , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Exposição Ambiental/efeitos adversos , Fibroblastos/química , Fibroblastos/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Dímeros de Pirimidina/química , Dímeros de Pirimidina/genética , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Raios Ultravioleta/efeitos adversos
5.
J Invest Dermatol ; 127(12): 2865-71, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17687389

RESUMO

Phototherapy with narrow-band UVB (NB-UVB), with a peak exclusively at 311 nm wavelength, has been found to be more effective in treating a variety of skin diseases than conventional broad-band UVB (BB-UVB). To assess the difference in carcinogenic activity between NB-UVB and BB-UVB, we investigated skin tumor formation by irradiating albino hairless, Ogg1 knockout mice and C57BL/6J wild counterparts with these two UV sources. We found that the ratio of malignant skin tumors induced by NB-UVB was significantly higher than that induced by BB-UVB. There was no significant difference in carcinogenicity of skin tumor induced by NB-UVB between Ogg1 knockout and wild-type mice. To investigate the possible cause of different carcinogenic activity by the different UV sources, we examined three types of DNA damage: cyclobutane pyrimidine dimer (CPD), (6-4) photoproduct, and 8-oxoguanine (8-oxoG) induced by each UV source. We found that CPD formation following a minimum erythema dose (MED) by NB-UVB was significantly higher than that following 1 MED by BB-UVB, whereas the formation of (6-4) photoproducts and 8-oxoG following BB-UVB was significantly higher than those following NB-UVB exposure. These results suggest that CPD formation is closely related to the higher carcinogenic characteristics of NB-UVB. JID JOURNAL CLUB ARTICLE: For questions, answers and open discussion about this article please go to http://network.nature.com/.


Assuntos
Transformação Celular Neoplásica , Ciclobutanos/química , DNA Glicosilases/genética , Epiderme/efeitos dos fármacos , Epiderme/efeitos da radiação , Fotoquímica/métodos , Dímeros de Pirimidina/química , Neoplasias Cutâneas/etiologia , Raios Ultravioleta , Animais , Guanosina/análogos & derivados , Guanosina/química , Humanos , Imuno-Histoquímica/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout
6.
Cell ; 83(5): 773-82, 1995 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-8521494

RESUMO

T4 endonuclease V is a DNA repair enzyme from bacteriophage T4 that catalyzes the first reaction step of the pyrimidine dimer-specific base excision repair pathway. The crystal structure of this enzyme complexed with a duplex DNA substrate, containing a thymine dimer, has been determined at 2.75 A resolution. The atomic structure of the complex reveals the unique conformation of the DNA duplex, which exhibits a sharp kink with a 60 degree inclination at the central thymine dimer. The adenine base complementary to the 5' side of the thymine dimer is completely flipped out of the DNA duplex and trapped in a cavity on the protein surface. These structural features allow an understanding of the catalytic mechanism and implicate a general mechanism of how other repair enzymes recognize damaged DNA duplexes.


Assuntos
Dano ao DNA , Reparo do DNA , Endodesoxirribonucleases/química , Conformação de Ácido Nucleico , Conformação Proteica , Dímeros de Pirimidina/química , Proteínas Virais , Adenina/química , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Desoxirribonuclease (Dímero de Pirimidina) , Endodesoxirribonucleases/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/síntese química , Oligodesoxirribonucleotídeos/metabolismo , Ligação Proteica , Dímeros de Pirimidina/metabolismo
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