title: PIDD orchestrates translesion DNA synthesis in response to UV irradiation.
abstract: PIDD has been implicated in survival and apoptotic pathways in response to DNA damage, and a role for PIDD was recently identified in non-homologous end-joining (NHEJ) repair induced by γ-irradiation. Here, we present an interaction of PIDD with PCNA, first identified in a proteomics screen. PCNA has essential functions in DNA replication and repair following UV irradiation. Translesion synthesis (TLS) is a process that prevents UV irradiation-induced replication blockage and is characterized by PCNA monoubiquitination and interaction with the TLS polymerase eta (polη). Both of these processes are inhibited by p21. We report that PIDD modulates p21-PCNA dissociation, and promotes PCNA monoubiquitination and interaction with polη in response to UV irradiation. Furthermore, PIDD deficiency leads to a defect in TLS that is associated, both in vitro and in vivo, with cellular sensitization to UV-induced apoptosis. Thus, PIDD performs key functions upon UV irradiation, including TLS, NHEJ, NF-κB activation and cell death.
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Logette
authors.forename: S
authors.initials: S
authors.lastname: Schuepbach-Mallepell
authors.forename: M J
authors.initials: MJ
authors.lastname: Eckert
authors.forename: X H
authors.initials: XH
authors.lastname: Leo
authors.forename: B
authors.initials: B
authors.lastname: Jaccard
authors.forename: C
authors.initials: C
authors.lastname: Manzl
authors.forename: A
authors.initials: A
authors.lastname: Tardivel
authors.forename: A
authors.initials: A
authors.lastname: Villunger
authors.forename: M
authors.initials: M
authors.lastname: Quadroni
authors.forename: O
authors.initials: O
authors.lastname: Gaide
authors.forename: J
authors.initials: J
authors.lastname: Tschopp
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis* / Q000235:genetics; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004261:DNA Replication / Q000235:genetics / Q000528:radiation effects*; D053418:Death Domain Receptor Signaling Adaptor Proteins; D005720:Gamma Rays; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D002352:Carrier Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D016328:NF-kappa B; C485896:PIDD1 protein, human; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA