title: Differential contribution of XPC, RAD23A, RAD23B and CENTRIN 2 to the UV-response in human cells.
abstract: Several genes in human cells are activated by physical genotoxic agents in order to regenerate cell homeostasis. Among the pathways contributing to this response, nucleotide excision repair (NER) is unique in restoring the nucleotide sequence of the DNA molecule without generating mutations. The first step of NER is mediated by a protein complex composed of XPC, RAD23B, an ubiquitin receptor and CENTRIN 2, an EF-hand calcium binding protein. These three proteins are multifunctional and participate in other important biochemical pathways. We silenced the XPC, RAD23A or RAD23B genes in HeLa cells for a long period of time by using Epstein Barr Virus-derived plasmids carrying sequences coding for small interfering RNA. XPC silencing confirms an essential role for XPC in DNA repair and cell survival after ultraviolet light irradiation. RAD23A and RAD23B participate in DNA repair and cell survival with diverging functions. Our data also indicate that CENTRIN 2 is recruited onto nuclear damaged areas quickly after irradiation and that XPC plays an important role during its internalization into the nucleus of human cells. Furthermore, the inhibition of XPC expression correlates with a decreased amount of CENTRIN 2 transcript and protein, indicating that XPC is required for the fine tuning of CENTRIN 2 gene expression. Moreover, XPC-silenced cells present a reduced concentration of CENTRIN 2 that affects both its centrosomal and nuclear localization suggesting that XPC deficiency may indirectly slow down cell division.
authors.affiliation: Laboratoire de Génétique de la Radiosensibilité, Institut de Radiobiologie Cellulaire et Moléculaire, CEA, Commissariat à l'Energie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, B.P. 6, 92265, Fontenay aux Roses, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Renaud
authors.forename: Laurent
authors.initials: L
authors.lastname: Miccoli
authors.forename: Natalie
authors.initials: N
authors.lastname: Zacal
authors.forename: Denis S
authors.initials: DS
authors.lastname: Biard
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Craescu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Rainbow
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Angulo
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D055550:Protein Stability; D021381:Protein Transport; D034622:RNA Interference; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C472752:CETN2 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C513287:RAD23B protein, human; C086985:RAD23A protein, human; C086984:XPC protein, human; D001616:beta-Galactosidase; D045643:DNA Repair Enzymes