title: The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner.
abstract: Retinoblastoma (Rb) protein promotes cell survival after DNA damage. We show here that the LxCxE binding site in Rb mediates both cell survival and cell-cycle arrest after DNA damage. Replication factor C (RF-C) complex plays an important role in DNA replication. We describe a novel function of the large subunit of RF-C in promoting cell survival after DNA damage. RF-Cp145 contains an LxCxE motif, and mutation of this motif abolishes the protective effect of RF-Cp145. The inability of wild-type RF-Cp145 to promote cell survival in Rb-null cells is rescued by Rb but not by Rb mutants defective in binding LxCxE proteins. RF-C thus enhances cell survival after DNA damage in an Rb-dependent manner.
authors.affiliation: Sidney Kimmel Cancer Center, 10835 Altman Road, San Diego, CA 92121, USA.
authors.forename: V
authors.initials: V
authors.lastname: Pennaneach
authors.forename: I
authors.initials: I
authors.lastname: Salles-Passador
authors.forename: A
authors.initials: A
authors.lastname: Munshi
authors.forename: H
authors.initials: H
authors.lastname: Brickner
authors.forename: K
authors.initials: K
authors.lastname: Regazzoni
authors.forename: F
authors.initials: F
authors.lastname: Dick
authors.forename: N
authors.initials: N
authors.lastname: Dyson
authors.forename: T T
authors.initials: TT
authors.lastname: Chen
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Fotedar
authors.forename: A
authors.initials: A
authors.lastname: Fotedar
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D019556:COS Cells; D002453:Cell Cycle / Q000235:genetics; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins; D006801:Humans; D015778:Minor Histocompatibility Antigens; D016296:Mutagenesis / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051818:Replication Protein C; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D002583:Uterine Cervical Neoplasms
chemical_list: C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D051818:Replication Protein C