title: DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks.
abstract: DNA double-strand break (DSB) repair interferes with ongoing cellular processes, including replication and transcription. Although the process of replication stalling upon collision of replication forks with damaged DNA has been extensively studied, the fate of elongating RNA polymerase II (RNAPII) that encounters a DSB is not well understood. We show that the occurrence of a single DSB at a human RNAPII-transcribed gene leads to inhibition of transcription elongation and reinitiation. Upon inhibition of DNA protein kinase (DNAPK), RNAPII bypasses the break and continues transcription elongation, suggesting that it is not the break per se that inhibits the processivity of RNAPII, but the activity of DNAPK. We also show that the mechanism of DNAPK-mediated transcription inhibition involves the proteasome-dependent pathway. The results point to the pivotal role of DNAPK activity in the eviction of RNAPII from DNA upon encountering a DNA lesion.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Université de Strasbourg, Illkirch, France.
authors.forename: Tibor
authors.initials: T
authors.lastname: Pankotai
authors.forename: Céline
authors.initials: C
authors.lastname: Bonhomme
authors.forename: David
authors.initials: D
authors.lastname: Chen
authors.forename: Evi
authors.initials: E
authors.lastname: Soutoglou
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D012319:RNA Polymerase II; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen