Regulation of RNA polymerase II-dependent transcription by poly(ADP-ribosyl)ation of transcription factors.
Poly(ADP-ribosyl) transferase (ADPRT) is a nuclear protein that modifies proteins by forming and attaching to them poly(ADP-ribose) chains. Poly(ADP-ribosyl)ation represents an event of major importance in perturbed cell nuclei and participates in the regulation of fundamental processes including DNA repair and transcription. Although ADPRT serves as a positive cofactor of transcription, initiation of its catalytic activity may cause repression of RNA polymerase II-dependent transcription. It is demonstrated here that ADPRT-dependent silencing of transcription involves ADP-ribosylation of the TATA-binding protein. This modification occurs only if poly(ADP-ribosyl)ation is initiated before TATA-binding protein has bound to DNA and thereby prevents formation of active transcription complexes. Specific DNA binding of other transcription factors including Yin Yang 1, p53, NFkappaB, Sp1, and CREB but not c-Jun or AP-2 is similarly affected. After assembly of transcription complexes initiation of poly(ADP-ribosyl)ation does not influence DNA binding of transcription factors. Accordingly, if bound to DNA, transcription factors are inaccessible to poly(ADP-ribosyl)ation. Thus, poly(ADP-ribosyl)ation prevents binding of transcription factors to DNA, whereas binding to DNA prevents their modification. Considering its ability to detect DNA strand breaks and stimulate DNA repair, it is proposed that ADPRT serves as a molecular switch between transcription and repair of DNA to avoid expression of damaged genes.
Oei
S L
SL
Institut für Biochemie, Freie Universität Berlin-Dahlem, Thielallee 63, D-14195 Berlin, Germany.
Griesenbeck
J
J
Schweiger
M
M
Ziegler
M
M
D036002:ADP Ribose Transferases / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D003001:Cloning, Molecular; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases; D012319:RNA Polymerase II / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016385:TATA Box; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050986:YY1 Transcription Factor; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases; D012319:RNA Polymerase II