Eukaryotic genome DNA is packaged into condensed chromatin, which creates a natural barrier for functional factors to access to DNA during replication, transcription, repair and recombination. Interactions of these factors with DNA require relaxation of local chromatin structure, and this type of chromatin dynamic alteration is called chromatin remodeling. Increasing evidences have indicated that chromatin remodeling plays key role in DNA damage repair by facilitating the recruitment of DNA damage response proteins to DNA lesions. To investigate the association between chromatin remodeling and DNA repair and its coupling mechanisms, a Lac-repressor and Lac-operator based system was employed. Through this system, the Lac repressor-target gene- EGFP fusion protein can bind to the Lac-operator elements integrated in the genome of AO3_1 cells, and potentially reflects the process of chromatin remodeling after DNA damage. Using this system, it was found that TIP60 strongly promotes the large scale chromatin relaxation, and the p53 inducible gene 3 protein (PIG3) can also promote the large scale chromatin relaxation in the process of cellular response to DNA damage induced by 10 Gy γ-ray irradiation. Taken together, an efficient method was established to screen potential chromatin remodeling proteins associating with DNA damage repair.