New insights in the difference between UV-sensitive syndrome and cockayne syndrome through new found functions for UVSSA and USP7 in transcription coupled repair

Abstract

DNA repair is an important mechanism in the cell to prevent mutations as a consequence of DNA damage, and possible adverse effects due to these mutations. There are several diseases known to be caused by defects in DNA repair pathways. Two of these diseases, UV sensitive syndrome and Cockayne syndrome, are caused by defects in transcription coupled repair, a sub pathway of nucleotide excision repair. Even though these diseases are caused by defects in the same pathway, their clinical manifestations differ greatly. UVSS patients show mild sun sensitivity, where CS patients show a more severe phenotype, including neurodegenerative symptoms. The causal distinction between these two diseases has been a mystery for a long time. Recently a new gene has been identified as the causal gene of UVSS, but not CS: UVSSA. Together with the DUB USP7, UVSSA might have an important role in the ubiquitin-regulation of TCR factors such as CSB. Mutations in CSB or CSA can cause Cockayne syndrome. It has been suggested that CSB and CSA might have different functions next to their role in TCR. The discovery of UVSSA and the new role of USP7 in TCR can shed a light on the distinction between UVSS and CS. Here I suggest that UVSSA only abolishes the function of CSB in TCR, but leaves CSB intact to fulfill its other functions, where in CS, CSB is dysfunctional in multiple processes, causing additional symptoms next to mild UV sensitivity.