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Sequence-specific DNA binding by Ku autoantigen and its effects on transcription
W Giffin1, H Torrance, D J Rodda
1Department of Medicine, University of Ottawa, Loeb Institute for Medical Research, Ottawa Civic Hospital, Ontario, Canada.
Nature
|March 21, 1996
Summary
The Ku autoantigen acts as a transcription factor, recruiting DNA-dependent protein kinase (DNA-PK) to specific DNA sequences. This binding represses viral gene expression by inhibiting MMTV transcription.
Area of Science:
- Molecular Biology
- Epigenetics
- Virology
Background:
- DNA-dependent protein kinase (DNA-PK) is crucial for nuclear processes like DNA repair and transcription.
- Ku autoantigen binds DNA ends and is essential for DNA-PK activity.
- The mechanism by which Ku binding leads to DNA-PK phosphorylation of DNA-binding proteins in vivo was unclear.
Purpose of the Study:
- To identify Ku as a transcription factor.
- To investigate how Ku recruits DNA-PK to specific DNA sequences.
- To determine the role of Ku/DNA-PK binding to NRE1 in MMTV transcription.
Main Methods:
- Identifying Ku as a transcription factor.
- Demonstrating Ku's recruitment of DNA-PK to specific DNA sequences.
- Analyzing the effect of Ku/DNA-PK binding to NRE1 on MMTV transcription.
Main Results:
- Ku was identified as a transcription factor that directly recruits DNA-PK to specific DNA sequences.
- Ku/DNA-PK binding to the NRE1 element in the MMTV LTR was demonstrated.
- This binding was shown to repress glucocorticoid-induced MMTV transcription.
Conclusions:
- Ku functions as a transcription factor, directly recruiting DNA-PK to specific DNA sites.
- The Ku/DNA-PK complex binding to NRE1 represses MMTV transcription.
- This provides a novel mechanism for regulating viral gene expression via DNA-PK.