Use of adenoviral vectors in the identification of genetic complementation group of patients with Xeroderma pigmentosum um and animals deficient in DNA repair.

Author(s)

Ricardo Alexandre Leite

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2008-09-30

Examining board members

Carlos Frederico Martins Menck; Januario Bispo Cabral Neto; Silvya Stuchi Maria Engler; Patricia Gama; Dewton de Moraes Vasconcelos

• Advisor: Carlos Frederico Martins Menck

Abstract

One of the most versatile mechanisms of DNA repair is the nucleotide excision repair (NER). Genetic defects in NER can generate different syndromes. Among these, Xeroderma pigmentosum) presents the highest sensitivity to sunlight, resulting in a large increase in the incidence of skin cancer, especially in areas exposed to the sunlight, and in some cases, progressive neurological degeneration and premature aging. In the first part of this project, adenoviral vectors carrying NER genes were used to identify genetic deficiency of three XP patients. The second part of work was extended to animal models, deficient for the same XP genes carried by adenoviral vectors. The genetic expression of vector was evaluated by detection of protein and EGFP fluorescence visualization in the skin of animals transduced. In summary, this work presents the use of adenovirus, carrying DNA repair genes for in vitro in vivo studies reports two deleterious mutations in Brazilian XP patients, including a new mutation. (AU)