title: Functional characterization of a mammalian transcription factor, Elongin A.
abstract: 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.
authors.affiliation: Department of Functional Genomics, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yasukawa
authors.forename: Kazuto
authors.initials: K
authors.lastname: Sugimura
authors.forename: Mizue
authors.initials: M
authors.lastname: Fukuda
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Kitajima
authors.forename: Katsuzumi
authors.initials: K
authors.lastname: Okumura
authors.forename: Teijiro
authors.initials: T
authors.lastname: Aso
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004261:DNA Replication; D000075065:Elongin; D005260:Female; D042822:Genomic Instability; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019913:Nuclear Localization Signals; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C000616403:Eloa protein, mouse; D000075065:Elongin; D019913:Nuclear Localization Signals; D014157:Transcription Factors; D012319:RNA Polymerase II