The role of CSA and CSB in the response to single and double strand breaks

A growing body of evidence indicate that the neurological defects in Cockayne Syndrome (CS) may be due to loss of mitochondrial function, whereas the impaired transcription-coupled repair could account for the skin photosensitivity. CS proteins have been involved in the repair of a wide variety of DNA lesions. Here, we analyze the role of CS proteins in DNA break repair by studying histone H2AX phosphorylation in different cell cycle phases and DNA break repair by comet assay in CSA and CSB cells. Following MMS treatment a significant accumulation of unrepaired SSB was detected in CS cells as compared to normal cells, leading to accumulation of DSB in S and G2 phases. A delay in DSB repair and accumulation in S and G2 phases was also observed following IR exposure. These data confirm the role of CSB in the suppression of NHEJ in S/G2 cells and extend this function to CSA. However, the repair kinetics of DSB showed unique features for CSA and CSB cells suggesting that these proteins may act at different times along the repair process. The involvement of CS proteins in DNA break repair may play an important role in the clinical features of CS patients.