CSB is a component of RNA pol I transcription.
Mutation in the CSB gene results in the human Cockayne's syndrome (CS). Here, we provide evidence that CSB is found not only in the nucleoplasm but also in the nucleolus within a complex (CSB IP/150) that contains RNA pol I, TFIIH, and XPG and promotes efficient rRNA synthesis. CSB is active in in vitro RNA pol I transcription and restores rRNA synthesis when transfected in CSB-deficient cells. We also show that mutations in CSB, as well as in XPB and XPD genes, all of which confer CS, disturb the RNA pol I/TFIIH interaction within the CSB IP/150. In addition to revealing an unanticipated function for CSB in rRNA synthesis, we show that the fragility of this complex could be one factor contributing to the CS phenotype.
Bradsher
John
J
Institut de Genetique et de Biologie Moleculaire et Cellulaire (CNRS/INSERM/ULP), F-67404, Illkirch Cedex, France.
Auriol
Jerome
J
Proietti de Santis
Luca
L
Iben
Sebastian
S
Vonesch
Jean Luc
JL
Grummt
Ingrid
I
Egly
Jean Marc
JM
D015153:Blotting, Western; D002466:Cell Nucleolus / Q000378:metabolism; D002478:Cells, Cultured; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D006801:Humans; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012318:RNA Polymerase I / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000096:biosynthesis; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII / Q000378:metabolism; D014158:Transcription, Genetic; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5
D004265:DNA Helicases; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; D012318:RNA Polymerase I; D012335:RNA, Ribosomal; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C078673:ERCC6 protein, human; C497292:ERCC2 protein, human