title: Transcription factor IIS impacts UV-inhibited transcription.
abstract: Inhibition of transcription elongation can cause severe developmental and neurological abnormalities notably manifested by the rare recessive progeroid disorder Cockayne syndrome (CS). DNA alterations can cause permanent blocks to an elongating RNA polymerase II (RNAPII) leading to transcriptional arrest. Abrogation of transcription arrest requires removal of transcription blocking lesions through transcription-coupled nucleotide excision repair (TC-NER) a process defective in CS. Transcription elongation factor IIS (TFIIS) has been found to localize with the TC-NER complex after cellular exposure to UV-C light and in vitro addition of TFIIS to a damage arrested RNAPII causes transcript shortening. Hence default TFIIS activity might mimic or contribute to the severe phenotype of Cockayne syndrome. Here we show that down regulation of TFIIS by siRNA treatment of human cells lead to impaired RNA synthesis recovery and elevated levels of hyper-phosphorylated RNAPII after UV-irradiation. TFIIS knock down does not affect TC-NER, the reappearance of hypo-phosphorylated RNAPII post-UV-irradiation, UV sensitivity or the p53 damage response. These findings reveal a role for TFIIS in transcription recovery and re-establishment of the balance between hypo- and hyper-phosphorylated RNAPII after DNA damage repair.
authors: Department of Toxicogenetics, Leiden University Medical Center, The Netherlands.
authors: Anne
authors: A
authors: Jensen
authors: Leon H F
authors: LH
authors: Mullenders
mesh_terms: D002460:Cell Line; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D010766:Phosphorylation / Q000528:radiation effects; D012313:RNA / Q000096:biosynthesis; D012319:RNA Polymerase II / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic / Q000528:radiation effects*; D035602:Transcriptional Elongation Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D034741:RNA, Small Interfering; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D012313:RNA; D012319:RNA Polymerase II