Advanced search
Start date
Betweenand

Understanding 3-methyladenine DNA glycosylase-mediated cell death in response to mitochondrial alkylation-damaged DNA

Grant number: 14/04165-7
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): August 01, 2014
Effective date (End): March 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Nadja Cristhina de Souza Pinto
Grantee:Carolina Maria Berra
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

DNA repair systems are ubiquitous and cross talk with diverse cellular machineries in order to protect and preserve the integrity of the genomes of all living organisms. However, DNA damage, resulting from the interaction between DNA and a variety of exogenous and endogenously generated agents, released as by-products from normal metabolic processes, cannot be avoided. In eukaryotic cells, damage is not confined to nuclear DNA, and mitochondrial DNA (mtDNA) is also exquisitely sensitive to damage. The base excision repair (BER) pathway is responsible for removing DNA bases modified by alkylating agents and reactive oxygen species (ROS), and is also the predominant repair system in the mitochondria. Defective or impaired BER has been implicated in several pathological conditions such as cancer, inflammation and neurological dysfunction as well as normal ageing. In mammals, 3-methyladenine DNA glycosylase (AAG) initiates the repair of alkylated DNA bases, playing an important role in protecting against the genotoxic effects of DNA alkylation damage. However, recent results have showed that animals and cells overexpressing AAG are hypersensitive to alkylating agents while knockout animals and cells are resistant, indicating that alkylation sensitivity can paradoxically be a direct result of AAG-initiated repair on alkylated substrates, influencing cellular homeostasis. This project aims to evaluate the contribution of alkylation damage in the mtDNA to the cell death process and determine whether the catalytic activity of AAG on these modifications generates the cell death signal.

News published in Agência FAPESP Newsletter about the scholarship:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list using this form.