Role of pol º e pol ¹¹ translesion synthesis polymerases in cell replication and survival after irradiation with UVC light

• Grant number: 20/15371-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2021
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Carlos Frederico Martins Menck
• Grantee: Abu-Bakr Adetayo Ariwoola
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg), AP.TEM

Abstract

The UVC light (200-280 nm) is absorbed by the DNA molecule generating mainly two types of lesions: cyclobutane pyrimidine dyes and photoproducts (6-4)-pyrimidine-pyrimidine, which distort the DNA tape. This damage, when not removed by DNA repair systems, can lead to the stop and, consequently, the collapse of the DNA replication fork. However, this phenomenon is avoided thanks to the presence of specialized DNA polymerases, capable of synthesizing DNA through the damage, giving the cell a certain tolerance to the lesion, in a process called translesion synthesis. The main objective of this project will be to evaluate the role of two specific translesion DNA polymerases (kappa polymerase, pol º, and polymerase iota, pol ¹ in cell replication and survival after irradiation of deficient cells for these polymerases. We have glioma knockout cell lines for polymerases in º or pol ¹, which will be evaluated initially for their sensitivity to irradiation with UVC light. Sensitivity to this irradiation may indicate the participation of these polymerases in the replication of DNA-induced lesions. Also, we intend to study the genotoxic stress caused in these cells and their impact on the induction of cell death. Besides, we will directly evaluate the activity of the replication fork against the lesions, through DNA fiber tests. Finally, as pol kappa has already been identified as responsible for DNA synthesis during lesion removal we intend to evaluate the contribution of these polymerases directly in the repair process of nucleotide excision of lesions caused by UVC light. (AU)