A role for Polycomb Repressive Complex 2 in the DNA damage response

Abstract

Polycomb protein methyltransferase, Enhancer of Zeste 2 (Ezh2), is frequently overexpressed in human malignancy and is implicated in cancer cell proliferation and invasion. Recently, several other polycomb proteins have been implicated in modulating the response to DNA double strand breaks, and thus we hypothesize that Ezh2 is also involved in the DNA damage response pathway. We investigated the involvement of Ezh2 and its associated complex, polycomb repressive complex 2 (PRC2), in the DNA damage response pathway. We found that PRC2 proteins recruit to sites of DNA damage and knockdown of Ezh2 decreases double strand break repair efficiency and increases cellular sensitivity to ionizing radiation. Our data supports the hypothesis that PRC2 is involved in the DNA damage response and contributes to DNA double strand break signaling and repair.