Transcription by RNA polymerase II in DNA-PK deficient scid mouse cells.
DNA-dependent protein kinase (DNA-PK) is involved in DNA repair but there is some evidence to suggest that it is also involved in regulating transcription. We used a pair of cell lines, SCVA2 and SC(8)-10, which are DNA-PK negative and positive respectively, in order to examine the effect of DNA-PK upon transcription. Initial experiments were performed using p53 as an activator of transcription because DNA-PK has been proposed as a candidate upstream activator of p53. It was found both in vivo and in vitro that efficient p53-dependent transcription required the presence of DNA-PK. However, phosphorylation of p53 by DNA-PK did not affect the DNA-binding ability of p53 nor its transcriptional activity when tested in vitro. Subsequent in vivo experiments suggested that a number of transcription activators functioned more efficiently in the presence of DNA-PK. Therefore DNA-PK may play a general role in regulation of transcription driven by RNA polymerase II. In addition, DNA-PK is shown to have no specific effect on p53-dependent transcription.
Sheppard
H M
HM
Department of Biochemistry, University of California, 92521, Riverside, CA, USA.
Liu
X
X
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014357:Trypsin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000494:pharmacology
D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D004247:DNA; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II; D014357:Trypsin