Is Interaction between p53 and p53-Binding Protein 1 (53BP1) Necessary for the Repair of DNA Double-Strand Breaks?

Abstract

After X-irradiation of cells, p53-binding protein 1 (53BP1) binds to chromatin at sites of DNA double-strand breaks in a phosphorylation-dependent manner. The Tudor plus Myb domain, the minimal region of 53BP1 for chromatin binding, binds directly to both double-stranded and single-stranded DNA, and stimulate end-joining by DNA ligase IV/Xrcc4, but not by T4 DNA ligase in vitro, suggesting 53BP1's role in the repair of DNA double-strand breaks. In the last meeting, we showed that a colon cancer cell line SW48 is deficient in 53BP1 expression, and that expression of 53BP1 in SW48 cells significantly reduce the number of cells containing X-ray-induced chromosomal aberrations. To determine whether 53BP1-p53 interaction is necessary for stimulation of repair by 53BP1 for X-ray-induced chromosomal aberrations, we established a SW48 cell line that expressed mutant 53BP1 that did not bind to p53. The importance of interaction between 53BP1 and p53 in the repair of DNA double-strand breaks will be discussed. [J Radiat Res 44:409 (2003)]