Functional characterization of a mammalian transcription factor, Elongin A

• Published in: Biochemical and biophysical research communications 2007-01, Vol.352 (1), p.237-243
• Main Authors: Yasukawa, Takashi, Sugimura, Kazuto, Fukuda, Mizue, Yamazaki, Katsuhisa, Kitajima, Shigetaka, Okumura, Katsuzumi, Aso, Teijiro
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; APOPTOSIS; Cells, Cultured; Cercopithecus aethiops; DNA; DNA Replication; ELONGATION; Elongin; Elongin A; EMBRYOS; Female; FIBROBLASTS; Genomic Instability; IN VIVO; INSTABILITY; INTERACTIONS; Male; MICE; Mice, Inbred C57BL; Mice, Knockout; Nuclear Localization Signals; PHENOTYPE; Protein Binding; Replication; RNA; RNA polymerase II; RNA Polymerase II - metabolism; STRUCTURE FUNCTIONS; TRANSCRIPTION; Transcription elongation; TRANSCRIPTION FACTORS; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.11.012

Elongin A is the transcriptionally active subunit of the Elongin complex that strongly stimulates the rate of elongation by RNA polymerase II (pol II) by suppressing the transient pausing of the polymerase at many sites along the DNA template. We have recently shown that Elongin A-deficient mice are embryonic lethal, and mouse embryonic fibroblasts (MEFs) derived from Elongin A −/− embryos display not only increased apoptosis but also senescence-like phenotypes accompanied by the activation of p53. To further understand the function of Elongin A in vivo, we have carried out the structure–function analysis of Elongin A and identified sequences critical to its nuclear localization and direct interaction with pol II. Moreover, we have analyzed the replication fork movement in wild-type and Elongin A −/− MEFs, and shown the possibility that the genomic instability observed in Elongin A −/− MEFs might be caused by the replication fork collapse due to Elongin A deficiency.