Banca de QUALIFICAÇÃO: LÁZARO BATISTA DE AZEVEDO MEDEIROS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : LÁZARO BATISTA DE AZEVEDO MEDEIROS
DATA : 28/05/2018
HORA: 08:00
LOCAL: Sala Carl Peter von Dietrich - Departamento de Bioquímica
TÍTULO:

THE ROLE OF XPA IN APE1, NFE2L2 AND PROTEASSOMA REGULATION AFTER INDUCTION OF DNA DAMAGE

PALAVRAS-CHAVES:

Oxidative stress; Base excision repair (BER); Nucleotide excision repair (NER); Xeroderma Pigmentosum; XPA; NFE2L2; proteasome

PÁGINAS: 94
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

During the cell cycle, reactive oxygen species (ROS) are generated mainly by normal mitochondrial activity. Among the ROS, hydrogen peroxide(H₂O₂) is considered to be one of the main agents in cellular processes such as redox homeostasis, cell signaling and redox regulation. H₂O₂ is an important signaling molecule involved in several transcriptional processes. Among transcriptional factors that are influenced by H₂O₂ levels, NFE2L2 plays a crucial role in cell adaptation in response to oxidative stress. Oxidative DNA damage is considered to be the main substrate for base excision repair (BER), but recent studies have shown that nucleotide excision repair pathway (NER) also plays a role in the repair of this type of damage. In this work, we analyzed the impactof XPA deficiency on the expression of regulatory genes involved in processes such as DNA repair, transcriptional regulation and ubiquitin-proteasome system activity. Therefore, XPA-deficient (XP12RO-SV) and proficient (XP12RO (XP-A)) cells were submitted to oxidative stress with H2O2 (500 µM) and it was observed that XPA-deficient cells presented a higher rate of late apoptosis in comparison to the proficient cell line. Otherwise, it was observed that there was no significant change in the mitochondrial membrane potential after the induction of oxidative stress. XPA-deficient cells presented elevated levels of NFE2L2 when compared to the proficient cell line and it was observed a decrease in the expression of the ubiquitin-proteasome EBE2E1 and UCHL1 genes in the deficient cells. XPA deficiency seems to promote the decrease in proteasome activity both at the endogenous level and after exposure to oxidative stress. Moreover, it was demonstrated a physical interaction between XPA and APE1 in human cells and the participation of NFE2L2 in the complex formed by XPA-APE1. This is the first study to propose an interaction between XPA, APE1 and NFE2L2, which suggests the XPA protein as a possible link between NER and BER pathways via interaction with APE1 protein. Such findings have not yet been reported in the literature and may contribute to a better understanding of the molecular mechanisms involving BER and NER patwhays in functions in molecular roles that transcend DNA repair.

MEMBROS DA BANCA:
Interno - 1149356 - ELIZEU ANTUNES DOS SANTOS
Presidente - 2261797 - TIRZAH BRAZ PETTA LAJUS
Interno - 1674709 - VIVIANE SOUZA DO AMARAL