Mitochondrial transcription factor A is the major protein in rodent hepatocytes that recognizes DNA lesions induced by N-acetoxy-acetylaminofluorene.
Extracts from rodent liver cells contain an abundant protein that recognizes DNA adducts induced by the chemical carcinogen N-acetoxy-acetylaminofluorene (AAAF). This protein also has a strong affinity for DNA damaged by cisplatin (DDP), but not by benzo(a)pyrene diolepoxide or UV-radiation, and has been termed AAAF/DDP-DDB. Here we purified this protein from rat tissue and analyzed it by mass spectrometry and identified it as mitochondrial transcription factor A (TFAM). Experiments with bacterially expressed recombinant TFAM confirmed its high affinity for DNA damaged by AAAF. Assuming its abundance and specificity for AAAF induced lesions, TFAM may significantly impede recognition and repair of DNA adducts induced by AAAF and other derivatives of 2-aminofluorene.
Pietrowska
Monika
M
Department of Experimental and Clinical Radiobiology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. m_pietrowska@io.gliwice.pl
Kołodziejczyk
Izabela
I
Widłak
Piotr
P
D000099:Acetoxyacetylaminofluorene / Q000009:adverse effects*; D000818:Animals; D018736:DNA Adducts; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000502:physiology*; D022781:Hepatocytes / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000302:isolation & purification / Q000502:physiology*; D051381:Rats; D014157:Transcription Factors / Q000302:isolation & purification / Q000502:physiology*
D018736:DNA Adducts; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D000099:Acetoxyacetylaminofluorene