Activation of p53 or loss of the Cockayne syndrome group B repair protein causes metaphase fragility of human U1, U2, and 5S genes.
Infection by adenovirus 12, transfection with the Ad12 E1B 55 kDa gene, or activation of p53 cause metaphase fragility of four loci (RNU1, PSU1, RNU2, and RN5S) each containing tandemly repeated genes for an abundant small RNA (U1, U2, and 5S RNA). We now show that loss of the Cockayne syndrome group B protein (CSB) or overexpression of the p53 carboxy-terminal domain induces fragility of the same loci; moreover, p53 interacts with CSB in vivo and in vitro. We propose that CSB functions as an elongation factor for transcription of structured RNAs, including some mRNAs. Activation of p53 would inhibit CSB, stalling transcription complexes and locally blocking chromatin condensation. Impaired transcription elongation may also explain the diverse clinical features of Cockayne syndrome.
Yu
A
A
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Fan
H Y
HY
Liao
D
D
Bailey
A D
AD
Weiner
A M
AM
D000107:Acetylation; D000256:Adenoviridae / Q000235:genetics; D002873:Chromosome Fragility; D003057:Cockayne Syndrome / Q000209:etiology / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes; D006801:Humans; D008677:Metaphase; D008957:Models, Genetic; D010446:Peptide Fragments / Q000235:genetics; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012342:RNA, Small Nuclear / Q000235:genetics*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D010446:Peptide Fragments; D000075223:Poly-ADP-Ribose Binding Proteins; D012342:RNA, Small Nuclear; D016159:Tumor Suppressor Protein p53; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes