The role of DNA damage and repair system protein XPC in activation and functions of dendritic cells

• Grant number: 23/09148-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Pedro Henrique Araujo Bandeira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

DNA undergoes daily damage from environmental, chemical, physical, and biological agents. These damages can be detected and repaired through specific repair pathways depending on the type of damage. One of the most important repair pathways involved in genetic maintenance is the nucleotide excision repair pathway, in which the XPC protein plays a role in lesion recognition and DNA strand pre-incision. Dendritic cells, important components of the immune system, act as mediators between the innate and adaptive immune responses when activated. They generate reactive oxygen species to combat pathogens and, through their metabolic state, they can also increase the production of these species via the mitochondrial pathway. Unneutralized reactive oxygen species can cause DNA damage, which, if left unrepaired, can be detected by the cytosolic DNA sensors in dendritic cells, leading to immune activation. Therefore, we believe that XPC is involved in the repair of DNA damage in dendritic cells caused by an excess of reactive oxygen species originating from the mitochondria. If this DNA damage is not repaired, it can trigger the activation of these cells. In this regard, we will investigate whether dendritic cells are activated in mice lacking the XPC protein. Our strategies will include examining the expression of activation markers using flow cytometry and ELISA, measuring increased DNA damage in XPC-deficient cells using the comet assay, and assessing whether the absence of XPC is associated with mitochondrial reactive oxygen species accumulation using MitoSOX, as well as studying alterations in cellular glycolytic metabolism.