Accession Number : ADA303827

Title :   Interaction of the Tumor Suppressor p53 with Replication Protein A.

Descriptive Note : Annual rept. 15 Jul 94-14 Jul 95,

Corporate Author : BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA

Personal Author(s) : Dutta, Anindya

PDF Url : ADA303827

Report Date : 15 JUL 1995

Pagination or Media Count : 21

Abstract : The DNA replication factor RPA physically associates with the tumor suppressor protein p53, an interaction that could be important for the function of both these proteins in normal and cancer cells. We have made small deletion fragments of the p53 protein and expressed them as GST-fusion proteins. These fragments showed that RPA binds to point mutations in p53. Two such mutant forms of p53 have the desired property of not binding RPA. Both these mutant versions of p53 retain wild type transcriptional activation property. Thus we are now in the position to use these mutant versions of p53 to test whether the RPA binding ability of p53 is important for its multiple functions. Deletion fragments of Rpal were made by in- vitro transcription translation to determine which parts of Rpal bound to p53. Binding to p53 requires a region of Rpal overlapping with the high affinity binding site for DNA explaining how p53 could competitively interfere with the DNA binding function of RPA. The evolutionarily conserved putative zinc finger near the C terminus of Rpal was not required for binding to p53.

Descriptors :   *DEOXYRIBONUCLEIC ACIDS, *MUTATIONS, *MAMMARY GLANDS, *BREAST CANCER, FUNCTIONS, POSITION(LOCATION), CELLS, PROTEINS, SITES, ZINC, CANCER, FINGERS.

Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology

Distribution Statement : APPROVED FOR PUBLIC RELEASE