Tatiana Grohmann Ortolan

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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.

Research Project

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. 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.


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.

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.

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.

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.

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.

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