DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells

DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.

► MSH2+ cells express hyperradiosensitivity.
► HRS in MSH2+ cells is associated with activation of the early G2-phase cell cycle check point.
► HRS is associated with persistent MRE11 and RAD51 foci after low dose irradiation.
► Low dose radiotherapy regimen could improve the treatment of MSH2 proficient tumors.
► MSH2 proficiency may reduce cancer susceptibility following exposure to low radiation doses.