DNA-repair factors of the Nucleotide -Excision-Repair (NER) pathway are part of the basal transcription apparatus of RNA polymerase I. Mutations in these factors can give rise to developmental disorders with symptoms that are typical for the aging body. Here we show that in Cockayne syndrome (CS) RNA polymerase I transcription elongation and the processing of the pre-rRNA are disturbed. The mature 18S rRNA is reduced and isolated ribosomes lack specific ribosomal proteins. Ribosomal proteins are susceptible to unfolding and the proteome of CS cells is heat-sensitive, indicating misfolded proteins and an error prone translation process in CS cells. Pharmaceutical chaperones restored impaired cellular proliferation. Thus, we provide evidence for severe malfunction in protein synthesis which together with a loss of proteostasis constitute the underlying pathophysiology in CS.