title: INO80 Chromatin Remodeler Facilitates Release of RNA Polymerase II from Chromatin for Ubiquitin-Mediated Proteasomal Degradation.
abstract: Stalling of RNA Polymerase II (RNAPII) on chromatin during transcriptional stress results in polyubiquitination and degradation of the largest subunit of RNAPII, Rpb1, by the ubiquitin proteasome system (UPS). Here, we report that the ATP-dependent chromatin remodeling complex INO80 is required for turnover of chromatin-bound RNAPII in yeast. INO80 interacts physically and functionally with Cdc48/p97/VCP, a component of UPS required for degradation of RNAPII. Cells lacking INO80 are defective in Rpb1 degradation and accumulate tightly bound ubiquitinated Rpb1 on chromatin. INO80 forms a ternary complex with RNAPII and Cdc48 and targets Rpb1 primed for degradation. The function of INO80 in RNAPII turnover is required for cell growth and survival during genotoxic stress. Our results identify INO80 as a bona fide component of the proteolytic pathway for RNAPII degradation and suggest that INO80 nucleosome remodeling activity promotes the dissociation of ubiquitinated Rpb1 from chromatin to protect the integrity of the genome.
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR3664, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Lafon
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR3664, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Surayya
authors.initials: S
authors.lastname: Taranum
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR3664, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: Institut Curie, PSL Research University, Laboratory of Proteomics and Mass Spectrometry, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dingli
authors.affiliation: Institut Curie, PSL Research University, Laboratory of Proteomics and Mass Spectrometry, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: UT MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, TX 78957, USA.
authors.forename: Sandipan
authors.initials: S
authors.lastname: Brahma
authors.affiliation: UT MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, TX 78957, USA.
authors.forename: Blaine
authors.initials: B
authors.lastname: Bartholomew
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR3664, 26 rue d'Ulm, 75248 Paris, France. Electronic address: manolis.papamichos@curie.fr.
authors.forename: Manolis
authors.initials: M
authors.lastname: Papamichos-Chronakis
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D016681:Genome, Fungal; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D054875:Ubiquitination; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; C483404:INO80 complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; C511736:RPB1 protein, S cerevisiae; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein