Research into the role of p53 in base excision repair in mitochondria of mammalian cells

• Grant number: 11/13553-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2011
• End date: March 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Valter Arthur
• Grantee: Felipe Augusto Godoy
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

All living organisms are constantly exposed to a variety of DNA damaging agents, leading to accumulation of chemical and structural modifications which can affect key processes such as replication and transcription. Various DNA repair pathways have evolved to deal with those modifications, thus preventing their toxic and mutational potential. Mutations in mtDNA are frequently observed in several diseases, which reflected in metabolic changes or even attenuation of apoptotic response to anticancer therapies. To maintain the integrity of mitochondrial genome, repair mechanisms are recruited to the organelle. Of these, the base excision repair (BER) pathway is the main pathway localized to mitochondria. In the nucleus, the tumor suppressor protein p53 contributes to maintaining DNA stability in part by stimulating BER. In response to certain stimuli, p53 translocates to mitochondria, where it can trigger an apoptotic response. However, we have demonstrated previously that p53 can stimulate the catalytic activity of the mitochondrial DNA polymerase, DNA polymerase gamma (pol ³), which participates both in the replication and repair of mtDNA. This project proposes to further characterize the role of p53 in modulating pol ³ activity during BER in human cells. For this, we propose: I) to investigate whether p53 associates physically pol ³; II) if the TFAM protein modulates the role of p53 in DNA repair in mitochondria, and III) the translocation of p53 to mitochondria is mediated by redox processes.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

GODOY, Felipe Augusto. Study of the role of p53 protein in base excision repair in mammalian cell mitochondria. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Pesquisas Energéticas e Nucleares (IPEN/BT) São Paulo.