Tatiana Grohmann Ortolan
From DNA Repair Lab
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| - | Eu sou Bacharel em Ciências Moleculares pela Universidade de São Paulo e obtive o meu Ph.D. pela Rutgers University/ University of Medicine and Dentistry of New Jersey. Estou no grupo desde setembro de 2005 e sou bolsista de pós-doutorado pela FAPESP. | + | I graduated from the Molecular Sciences Course at the University of São Paulo, and got my Ph.D. from a joint program between Rutgers University and the University of Medicine and Dentistry of New Jersey. I´m supported by a Postdoctoral Fellowship from FAPESP since Sptember 2005. |
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| - | == Resumo do Projeto == | + | == Research Project == |
| - | O componente ultravioleta (UV) da luz solar é um notório carcinógeno ambiental que induz danos no DNA, sendo que estes podem interferir com os processos de replicação e transcrição. O reparo por excisão de nucleotídeos (NER) é o principal mecanismo para a remoção desses danos. | + | The ultraviolet (UV) component of the solar radiation is a notorious environmental carcinogen that induces DNA damage which can interfere with the replication and transcription processes. The nucleotide excision repair (NER) pathway is the main mechanism for the removal of these kinds of damage. |
| - | Organismos multicelulares recorrem ao suicídio celular, ou apoptose, para evitar os efeitos deletérios da presença de uma quantidade excessiva ou irreparável de danos no DNA. A proteína p53 é um fator ativador de transcrição que tem um lugar central no processo decisório das células humanas entre vida ou morte. Na presença de danos no DNA, o acúmulo da p53 leva à ativação de genes pró-apoptóticos, assim como o da Mdm2, uma proteína que estimula a degradação e inibe a atividade transcricional da p53. A presença de lesões em regiões transcritas do genoma tem uma função crítica na sinalização de apoptose após irradiação com UV, pelo menos em parte por afetar a expressão de genes envolvidos na regulação e indução de apoptose. | + | Multi-cellular organisms recur to cellular suicide, or apoptosis, to avoid the deleterious effects of the presence of an excessive or irreparable amount of damage to the DNA. The transcription factor p53 has a central role in the cellular decision between life and death. In the presence of DNA lesions, accumulation of p53 leads to the activation of pro-apoptotic genes, including that coding for Mdm2, a protein that stimulates the degradation and inhibits the transcriptional activity of p53. The presence of lesions in transcribed regions of the genome has a critical function for signaling of apoptosis after UV irradiation, at least in part by affecting the expression of the genes involved in the regulation and induction of apoptosis. |
| - | Segundo modelos genéricos, a indução de apoptose é determinada pela incapacidade das células de encerrar a atividade da p53 antes que um limiar apoptótico seja atingido. A minha pesquisa está fazendo uso de culturas primárias de fibroblastos humanos, proficientes ou deficientes em NER, e irradiadas com UVB, para testar o modelo genérico acima e para clarificar o papel da Mdm2 na sinalização de apoptose. Além disso, variações temporais nos níveis de proteínas ou modificações pós-traducionais associadas à presença de lesões no DNA serão exploradas em diferentes condições. Esta abordagem ajudará a distinguir as contribuições específicas dos danos presentes em regiões transcritas ou não transcritas do genoma, assim como dos bloqueios de replicação, para o processo apoptótico. | + | According to general models, the induction of apoptosis is determined by the cells´inability to end the p53 response before an apoptotic threshold is reached. My research is making use of cultured primary human fibroblasts, both proficient and deficient in NER, to test that general model and to clarify the role of Mdm2 in apoptosis signaling after UVB treatment. In addition to that, temporal variations in the protein levels and post-translational modifications associated to the presence of DNA lesion are being explored in different conditions. This approach is helping us to distinguish the specific contributions of the lesions present in transcribed or non-transcribed regions of the genome, as well as that of the replication blocks, to the apoptotic process. |
| - | ==Publicações== | + | ==Publications== |
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| - | |}Ortolan, T.G., Chen, L., Tongaonkar, P., and Madura, K. (2004) Rad23 stabilizes Rad4 from degradation by the Ub/proteasome pathway. Nucleic Acids Res. 32: 6490-500. | + | [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=18440285&query_hl=4&itool=pubmed_DocSum Carvalho H, '''ORTOLAN TG''', dePaula T, Leite RA, Weinlich R, Amarante-Mendes GP and Menck CF] (2008) Sustained activation of p53 in confluent nucleotide excision repair-deficient cells resistant to ultraviolet-induced apoptosis. ''DNA Repair''. 7:922-31. <br><br> |
| - | + | [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15601997&query_hl=4&itool=pubmed_DocSum '''ORTOLAN TG''', Chen L, Tongaonkar P and Madura K] (2004) Rad23 stabilizes Rad4 from degradation by the Ub/proteasome pathway. ''Nucleic Acids Res''. 32: 6490-500. <br><br> | |
| - | Lommel, L., Ortolan, T., Chen, L., Madura, K., and Sweder, K.S. (2002) Proteolysis of a nucleotide excision repair protein by the 26S proteasome. Curr Genet. 42: 9-20. | + | [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12420141&query_hl=4&itool=pubmed_DocSum Lommel L, '''ORTOLAN T''', Chen L, Madura K and Sweder KS] (2002) Proteolysis of a nucleotide excision repair protein by the 26S proteasome. ''Curr Genet''. 42: 9-20. <br><br> |
| - | + | [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11571271&query_hl=4&itool=pubmed_DocSum Chen L, Shinde U, '''ORTOLAN TG''' and Madura K] (2001) Ubiquitin-associated (UBA) domains in Rad23 bind ubiquitin and promote inhibition of multi-ubiquitin chain assembly. ''EMBO Rep''. 2: 933-8. <br><br> | |
| - | Chen, L., Shinde, U., Ortolan, T.G., and Madura, K. (2001) Ubiquitin-associated (UBA) domains in Rad23 bind ubiquitin and promote inhibition of multi-ubiquitin chain assembly. EMBO Rep. 2: 933-8. | + | [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10980700&query_hl=4&itool=pubmed_DocSum'''ORTOLAN, TG''', Tongaonkar P, Lambertson D, Chen L, Schauber C and Madura K] (2000) The DNA repair protein Rad23 is a negative regulator of multi-ubiquitin chain assembly. ''Nat Cell Biol''. 2: 601-8. <br><br> |
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| - | Ortolan, T.G., Tongaonkar, P., Lambertson, D., Chen, L., Schauber, C., and Madura, K. (2000) The DNA repair protein Rad23 is a negative regulator of multi-ubiquitin chain assembly. Nat Cell Biol. 2: 601-8. | + | |
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| - | Ortolan, T.G. (2004) Rad23 regulates the stability of Rad4: Understanding the connection between DNA repair and the ubiquitin-proteasome system. Piscataway, NJ. Tese de Doutorado, UMDNJ. | + | |
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I graduated from the Molecular Sciences Course at the University of São Paulo, and got my Ph.D. from a joint program between Rutgers University and the University of Medicine and Dentistry of New Jersey. I´m supported by a Postdoctoral Fellowship from FAPESP since Sptember 2005. |
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[edit] Research ProjectThe ultraviolet (UV) component of the solar radiation is a notorious environmental carcinogen that induces DNA damage which can interfere with the replication and transcription processes. The nucleotide excision repair (NER) pathway is the main mechanism for the removal of these kinds of damage. Multi-cellular organisms recur to cellular suicide, or apoptosis, to avoid the deleterious effects of the presence of an excessive or irreparable amount of damage to the DNA. The transcription factor p53 has a central role in the cellular decision between life and death. In the presence of DNA lesions, accumulation of p53 leads to the activation of pro-apoptotic genes, including that coding for Mdm2, a protein that stimulates the degradation and inhibits the transcriptional activity of p53. The presence of lesions in transcribed regions of the genome has a critical function for signaling of apoptosis after UV irradiation, at least in part by affecting the expression of the genes involved in the regulation and induction of apoptosis. According to general models, the induction of apoptosis is determined by the cells´inability to end the p53 response before an apoptotic threshold is reached. My research is making use of cultured primary human fibroblasts, both proficient and deficient in NER, to test that general model and to clarify the role of Mdm2 in apoptosis signaling after UVB treatment. In addition to that, temporal variations in the protein levels and post-translational modifications associated to the presence of DNA lesion are being explored in different conditions. This approach is helping us to distinguish the specific contributions of the lesions present in transcribed or non-transcribed regions of the genome, as well as that of the replication blocks, to the apoptotic process. [edit] Publications
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