The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner

Mol Cell. 2001 Apr;7(4):715-27. doi: 10.1016/s1097-2765(01)00217-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites / physiology
  • COS Cells
  • Cell Cycle / genetics
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • DNA Damage / genetics*
  • DNA Helicases
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Histone Deacetylase 1
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Homeodomain Proteins*
  • Humans
  • Minor Histocompatibility Antigens
  • Mutagenesis / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Replication Protein C
  • Repressor Proteins*
  • Retinoblastoma Protein / genetics*
  • Retinoblastoma Protein / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Ultraviolet Rays
  • Uterine Cervical Neoplasms

Substances

  • BCL2-related protein A1
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • MATA1 protein, S cerevisiae
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Repressor Proteins
  • Retinoblastoma Protein
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases
  • SMARCA4 protein, human
  • DNA Helicases
  • Replication Protein C