Cell Cycle Manipulation in Breast Cancer: Implications for Improved Therapy.
Abstract
In addition to binding DNA in a sequence-specific manner, p53 can interact with nucleic acids in a sequence-independent manner. p53 can bind short single-stranded DNA and double-stranded DNA containing nucleotide loops; these diverse associations may be critical for p53 signal transduction in breast cells. In this study, we are analyzing p53 binding to DNA fragments containing insertion/deletion mismatches (IDLs). p53 required an intact central domain and dimerization domain for high affinity complex formation with IDLs. From saturation binding studies we determined that the KD of p53 binding to IDLs was 2.1 nM as compared to a KD of 0.3 nM for p53 binding to DNA fragments containing a consensus binding site. Consistent with these dissociation constants, p53-IDL complexes were dissociated with relatively low concentrations of competitor consensus site-containing DNA. The relative number and availability of each form of DNA in a cell immediately after DNA damage may promote p53 interaction with DNA lesions. Understanding how the sequence-specific and non-specific DNA binding activities of p53 are integrated will contribute to our knowledge of how signaling cascades are initiated after DNA damage in breast cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA356205
Entities
People
- Suzanne Szak
Organizations
- Vanderbilt University Medical Center