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

Autor: Heather Torrance, Ward Giffin, Louise Pope, Robert J. G. Haché, David J. Rodda, Gratien G. Prefontaine
Rok vydání: 1996
Předmět:
Zdroj: Nature. 380:265-268
ISSN: 1476-4687
0028-0836
DOI: 10.1038/380265a0
Popis: DNA-dependent protein kinase (DNA-PK) has been implicated in several nuclear processes including transcription, DNA replication, double-stranded DNA break repair, and V(D)J recombination. Linkage of kinase and substrate on DNA in cis is required for efficient phosphorylation. Recruitment of DNA-PK to DNA is by Ku autoantigen, a DNA-end-binding protein required for DNA-PK catalytic activity. Although Ku is known to translocate along naked DNA, 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. We show that direct binding of Ku/DNA-PK to NRE1 represses glucocorticoid-induced MMTV transcription.
Databáze: OpenAIRE