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Atomic force microscopy reveals kinks in the p53 response element DNA.
P Balagurumoorthy1, Stuart M Lindsay, Rodney E Harrington
1Department of Microbiology, Arizona State University, Tempe, AZ 85287, USA. balaguru@asu.edu
Biophysical Chemistry
|December 19, 2002
Summary
The tumor suppressor p53 protein recognizes DNA response elements. Specific DNA sequences, like d(CATG.CATG), create kinks, enhancing p53 tetramer binding and complex stability.
Area of Science:
- Molecular Biology
- Structural Biology
- Genetics
Background:
- The p53 protein, a critical tumor suppressor, functions by binding to specific DNA sequences.
- p53 acts as a tetramer, meaning four p53 protein units bind to DNA together.
- Understanding the DNA structural features that govern p53 recognition is key to its tumor suppressor function.
Purpose of the Study:
- To investigate the structural basis of DNA recognition by the p53 protein.
- To compare the intrinsic flexibility of different p53 response elements.
- To elucidate how DNA sequence dictates p53 tetramer binding and complex stability.
Main Methods:
- Comparative analysis of DNA flexibility using ring closure models.
- Atomic force microscopy (AFM) of circularized DNA oligomers to visualize structural features.
- Sequence analysis of naturally occurring p53 response elements.
Main Results:
- DNA sequences with central d(CATG.CATG) are more flexible and prone to bending than those with d(CTTG.CTTG).
- More flexible DNA binding sites containing d(CATG.CATG) show increased affinity for p53 tetrameric binding.
- Atomic force microscopy revealed sequence-specific kinks in DNA structures in solution.
Conclusions:
- The d(CATG.CATG) sequence introduces sequence-specific kinks in p53 response elements.
- These kinks are a common structural theme in functional p53 binding sites.
- DNA-induced structural features, particularly kinks from d(CATG.CATG), are crucial determinants for p53 binding site recognition and complex stability.