Characterization of molecular mechanisms of DNA repair in mouse olfactory epithelium

• Grant number: 17/13723-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2017
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Nadja Cristhina de Souza Pinto
• Grantee: Fernanda Teixeira Rowies
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The perception of smells begins with the correct identification of odorants by olfactory sensory neurons (OSNs), through their receptors. Each OSN expresses a single type of receptor, making olfactory response quite specific. OSNs are very peculiar, when compared to other types of neurons, as they have shorter lifespan and are constantly replaced throughout the life of an individual (undergoing maturation and migration across the olfactory epithelium), whereas other types of neurons are known for being irreplaceable and having a much longer lifespan. Furthermore, the nuclear architecture is different in OSNs from that in most mammal cells as heterochromatin regions are located in the nucleus center, whereas euchromatin regions are in the nucleus periphery. Recent studies demonstrate that DNA repair depends on nuclear architecture. However, little is known about the effect of OSNs nuclear architecture on DNA repair activity in these cells. DNA repair plays a pivotal role in genomic integrity and defects in such pathway lead to accumulation of damaged DNA and genomic instability, which can lead to cancer, aging and neurodegeneration. Results from our group and others indicate that DNA repair defects are associated with Alzheimer's disease, and loss of olfactory function is an early symptom of this condition, which is, in fact, often used as treatment response marker. Nonetheless, no data is available in the literature on DNA repair activities in OSNs. Thus, the aim of this project is to characterize, describe and compare DNA repair pathways in OSNs as a function of its nuclear architecture and stage of maturation. Preliminary results suggest that, in mature OSNs, expression of homologous recombination (HR) pathway proteins is diminished. This pathway is responsible for double strand breaks (DSBs) repair (the most toxic type of lesion) in a homology-dependent mechanism. On the other hand, expression of non-homologous end joining (NHEJ) components, which repair DSBs in a homology-independent fashion, is increased in mature OSNs when compared to progenitors. These results suggest a compensatory balance between the two pathways, so that the lesions can be repaired as cell exit cell cycle and no homology is available. (AU)

Academic Publications

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

ROWIES, Fernanda Teixeira. Molecular characterization of DNA repair in mouse olfactory epithelium. 2019. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.