Clearance of DNA damage-arrested RNAPII is selectively impaired in Cockayne syndrome cells
van der Meer, P. J.; Yakoub, G.; Nakazawa, Y.; Ogi, T.; Luijsterburg, M.
Show abstract
Arrest of elongating RNA polymerase II (RNAPII) at DNA lesions initiates transcription-coupled repair (TCR), involving the concerted action of specific TCR factors, followed by downstream nucleotide excision repair steps. Remarkedly, only congenital defects in the CSA or CSB genes cause the neurodegenerative disorder Cockayne syndrome, which is not observed with other TCR genes, despite their equal importance in TCR. An explanation for this discrepancy has been lacking. In this study, we developed an assay to track the fate of elongating RNAPII at sites of UV-induced DNA lesions. Employing this method on an isogenic collection of TCR knockout cells reveals a selective RNAPII clearance defect in cells defective in CSA or CSB, in contrast to knockouts of other TCR genes. Our findings provide evidence that a deficiency in RNAPII processing and prolonged transcription arrests in response to DNA damage, rather than compromised DNA repair, may underlie the Cockayne syndrome-like neurodegenerative phenotype.
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