Translator Disclaimer
1 March 2011 Protein-Protein Interactions Occur Between p53 Phosphoforms and ATM and 53BP1 at Sites of Exogenous DNA Damage
Shahnaz T. Al Rashid, Shane M. Harding, Cindy Law, Carla Coackley, Robert G. Bristow
Author Affiliations +
Abstract

We have previously shown that the Ser15-phosphorylated p53 phosphoform, p53Ser15, can localize at sites of ionizing radiation-induced DNA damage. In this study, we hypothesized that the non-specific DNA binding domain (NSDBD) of the p53 carboxy-terminus (C-terminus) mediates chromatin anchoring at sites of DNA damage to interact with two key mediators of the DNA damage response (DDR): ATM and 53BP1. Exogenous YFP-p53 fusion constructs expressing C-terminus deletion mutants of p53 were transfected into p53-null H1299 cells and tracked by microscopy and biochemistry to determine relative chromatin-binding pre- and postirradiation. We observed that exogenous YFP-p53WT and YFP-p53Δ367–393 associated with ATMSer1981 and 53BP1 in the nuclear, chromatin-bound fractions after DNA damage. Of interest, YFP-p53Δ1–299 fusion proteins, which lack transcriptional trans-activation and the Ser15-residue, bound to ATMSer1981 but not to 53BP1. In support of these data, we used subnuclear UV-microbeam and immunoprecipitation analyses of irradiated normal human fibroblasts (HDFs) that confirmed an interaction between endogenous p53 and ATM or 53BP1. Based on these observations, we propose a model whereby a pre-existing pool of p53 responds immediately to radiation-induced DNA damage using the C-terminus to spatially facilitate protein-protein interactions and the DDR at sites of DNA damage.

Shahnaz T. Al Rashid, Shane M. Harding, Cindy Law, Carla Coackley, and Robert G. Bristow "Protein-Protein Interactions Occur Between p53 Phosphoforms and ATM and 53BP1 at Sites of Exogenous DNA Damage," Radiation Research 175(5), 588-598, (1 March 2011). https://doi.org/10.1667/RR2084.1
Received: 17 November 2009; Accepted: 1 January 2011; Published: 1 March 2011
JOURNAL ARTICLE
11 PAGES


Share
SHARE
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top