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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Animals
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Binding Sites / physiology
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COS Cells
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Cell Cycle / genetics
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Cell Survival / genetics
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Cell Survival / radiation effects
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DNA Damage / genetics*
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DNA Helicases
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism*
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Female
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Histone Deacetylase 1
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism
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Homeodomain Proteins*
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Humans
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Minor Histocompatibility Antigens
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Mutagenesis / physiology
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2*
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Replication Protein C
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Repressor Proteins*
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Retinoblastoma Protein / genetics*
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Retinoblastoma Protein / metabolism*
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Saccharomyces cerevisiae Proteins*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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Tumor Cells, Cultured
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Ultraviolet Rays
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Uterine Cervical Neoplasms
Substances
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BCL2-related protein A1
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DNA-Binding Proteins
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Homeodomain Proteins
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MATA1 protein, S cerevisiae
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Minor Histocompatibility Antigens
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Nuclear Proteins
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Proto-Oncogene Proteins c-bcl-2
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Repressor Proteins
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Retinoblastoma Protein
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylases
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SMARCA4 protein, human
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DNA Helicases
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Replication Protein C