期刊
CELL CYCLE
卷 13, 期 13, 页码 2029-2037出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.29018
关键词
Cockayne syndrome; RNA polymerase I transcription; DNA repair; premature aging; growth; ribosomopathy
类别
资金
- German Research Foundation DFG [IB 83/2-2, IB 83/3-1]
- Perspektivforderung of Baden-Wuerttemberg
Mutations in the Cockayne syndrome A (CSA) protein account for 20% of Cockayne syndrome (CS) cases, a childhood disorder of premature aging and early death. Hitherto, CSA has exclusively been described as DNA repair factor of the transcription-coupled branch of nucleotide excision repair. Here we show a novel function of CSA as transcription factor of RNA polymerase I in the nucleolus. Knockdown of CSA reduces pre-rRNA synthesis by RNA polymerase I. CSA associates with RNA polymerase I and the active fraction of the rDNA and stimulates re-initiation of rDNA transcription by recruiting the Cockayne syndrome proteins TFIIH and CSB. Moreover, compared with CSA deficient parental CS cells, CSA transfected CS cells reveal significantly more rRNA with induced growth and enhanced global translation. A previously unknown global dysregulation of ribosomal biogenesis most likely contributes to the reduced growth and premature aging of CS patients.
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