Roles of MSH2 and MSH6 in cadmium-induced G2/M checkpoint arrest in Arabidopsis roots.

ABSTRACT

DNA mismatch repair (MMR) proteins have been implicated in sensing and correcting DNA damage, and in governing cell cycle progression in the presence of structurally anomalous nucleotide lesions induced by different stresses in mammalian cells. Here, Arabidopsis seedlings were grown hydroponically on 0.5 × MS media containing cadmium (Cd) at 0-4.0 mg L-1 for 5 d. Flow cytometry results indicated that Cd stress induced a G2/M cell cycle arrest both in MLH1-, MSH2-, MSH6-deficient, and in WT roots, associated with marked changes of G2/M regulatory genes, including ATM, ATR, SOG1, BRCA1, WEE1, CYCD4; 1, MAD2, CDKA;1, CYCB1; 2 and CYCB1; 1. However, the Cd-induced G2/M phase arrest was markedly diminished in the MSH2- and MSH6-deficient roots, while a lack of MLH1 had no effect on Cd-induced G2 phase arrest relative to that in the wild type roots under the corresponding Cd stress. Expression of the above G2/M regulatory genes was altered in MLH1, MSH2 and MSH6-deficient roots in response to Cd treatment. Furthermore, Cd elicited endoreplication in MSH2- and MSH6-deficient roots, but not in MLH1-deficient Arabidopsis roots. Results suggest that MSH2 and MSH6 may act as direct sensors of Cd-mediated DNA damage. Taken together, we conclude that MSH2 and MSH6, but not MLH1, components of the MMR system are involved in the G2 phase arrest and endoreplication induced by Cd stress in Arabidopsis roots.