The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner.
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.
Pennaneach
V
V
Sidney Kimmel Cancer Center, 10835 Altman Road, San Diego, CA 92121, USA.
Salles-Passador
I
I
Munshi
A
A
Brickner
H
H
Regazzoni
K
K
Dick
F
F
Dyson
N
N
Chen
T T
TT
Wang
J Y
JY
Fotedar
R
R
Fotedar
A
A
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
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