Transcription-positive cofactor 4 forms complexes with HSSB (RPA) on single-stranded DNA and influences HSSB-dependent enzymatic synthesis of simian virus 40 DNA.
The replication of simian virus 40 (SV40) DNA in vitro requires a trimeric single-stranded DNA (ssDNA)-binding protein called HSSB or RPA. HSSB supports the unwinding of DNA containing the SV40 origin in the presence of the viral-encoded T antigen and is required for the initiation of RNA primer synthesis as well as processive elongation of DNA catalyzed by the DNA polymerase delta holoenzyme. In this report we show that the transcription positive cofactor 4 (PC4), a ssDNA-binding protein, forms complexes with HSSB on ssDNA and markedly affects the replication functions of HSSB. PC4 supports T antigen-catalyzed unwinding of SV40 origins in lieu of HSSB but inhibits both RNA primer synthesis and polymerase delta-catalyzed DNA chain elongation reactions. These inhibitory effects can be reversed by the addition of excess HSSB. Depending on the concentration of HSSB, PC4 is capable of either inhibiting or activating SV40 DNA replication measured in both mono- and dipolymerase systems. The possible role of PC4 in the initiation of DNA replication is discussed.
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Derald H. Ruttenberg Cancer Center, The Mount Sinai Medical Center, New York, New York 10029-6574, USA.
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Hurwitz
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D000957:Antigens, Viral, Tumor / Q000494:pharmacology; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D019915:DNA Primase; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015751:Genes, pol; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009843:Oligoribonucleotides / Q000096:biosynthesis; D012316:RNA Nucleotidyltransferases / Q000378:metabolism; D051716:Replication Protein A; D012097:Repressor Proteins; D013539:Simian virus 40 / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication
D000957:Antigens, Viral, Tumor; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C022262:Okazaki fragments; D009843:Oligoribonucleotides; D051716:Replication Protein A; D012097:Repressor Proteins; D015534:Trans-Activators; D004247:DNA; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; D004265:DNA Helicases