CELL RESPONSES FROM COCKAYNE SYNDROME PATIENTS TO DNA DAMAGE CAUSED BY UVB LIGHT AND FORMALDEHYDE

Abstract

Cockayne Syndrome (CS) is a genetic neurodegenerative disease related to the impairment of the transcription-coupled repair sub-pathway (TCR-NER). The CSB protein acts directly on this repair subpathway and, therefore, CSB mutant cells are more sensitive to agents that cause DNA damage. The greater sensitivity of these cells to UV light, an agent that damage DNA, is well known, however, experiments so far have used light of the UVC wavelengths (260 nm) to irradiate the cells. In this work, we intend to use UVB light (280-320 nm) seeking to identify specific characteristics, especially because these wavelengths are found in the sunlight that reaches us. Parallel to irradiation with UVB light, we will also test cells treated with formaldehyde, since this substance has recently been indicated as an important source of DNA damage similar to endogenous lesions. It is important to point out that endogenous DNA damage is probably correlated with the clinical symptoms of CSB patients, mainly neurodegeneration and premature aging. As nucleotide excision repair (NER) repairs lesions that block the progress of the transcription machinery, this work proposes to characterize the responses of CSB cells irradiated with UVB light and treated with formaldehyde, therefore, evaluating the effects on cell viability and survival, in addition to effects on cell cycle progression due to those potential transcription blocks.