Sequence-specific DNA binding by Ku autoantigen and its effects on transcription

• Published in: Nature (London) 1996-03, Vol.380 (6571), p.265-268
• Main Authors: Giffin, Ward, Torrance, Heather, Rodda, David J, Préfontaine, Gratien G, Pope, Louise, Haché, Robert J. G
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Nuclear; Autoantigens - metabolism; Base Sequence; Biochemistry; Biological and medical sciences; Cell Line; Cricetinae; Cricetulus; Deoxyribonucleic acid; DNA; DNA Helicases; DNA, Viral - metabolism; DNA-Activated Protein Kinase; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Ku Autoantigen; letter; Mammary Tumor Virus, Mouse - genetics; Mice; Mice, SCID; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mouse mammary tumor virus; multidisciplinary; Nuclear Proteins - metabolism; Phosphorylation; Plasmids; Protein Binding; Protein-Serine-Threonine Kinases - metabolism; Proteins; Repetitive Sequences, Nucleic Acid; Science; Science (multidisciplinary); Transcription Factors - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/380265a0

DNA-DEPENDENT protein kinase (DNA-PK) has been implicated in several nuclear processes including transcription 1–3 , DNA replication 4,5 , double-stranded DNA break repair, and V(D) J recombination 6–10 . Linkage of kinase and substrate on DNA in cis is required for efficient phosphorylation 11 . Recruitment of DNA-PK to DNA is by Ku autoantigen, a DNA-end-binding protein required for DNA-PK catalytic activity 11 . Although Ku is known to translocate along naked DNA 12 , how DNA-end binding by Ku might lead to DNA-PK-mediated phosphorylation of sequence-specific DNA-binding proteins in vivo has not been obvious. Here we report the identification of Ku as a transcription factor that recruits DNA-PK directly to specific DNA sequences. NRE1 (negative regulatory element 1) is a DNA sequence element (−394/ − 381) in the long terminal repeat of mouse mammary tumour virus (MMTV) that is important for repressing inappropriate viral expression 13–16 . We show that direct binding of Ku/DNA-PK to NRE1 represses glucocorticoid-induced MMTV transcription.