Figure 6

Proposed model for the role of SMAR1 in IR-induced DNA damage repair. (a) SMAR1 forms a triple complex with Ku70 and HDAC6, thus maintains Ku70 in a deacetylated state. Upon IR, SMAR1 gets phosphorylated by ATM at Ser370 and favors the recruitment of deacetylated Ku70 to the DSB sites. Moreover, SMAR1 also favors G2/M arrest, thus providing damaged cells ample time for efficient repair. On the other hand, deacetylated Ku70 interacts with Bax and regulates Bax-mediated apoptosis. (b) SMAR1 knockdown results in increased acetylation of Ku70 due to perturbation of triple complex between SMAR1, Ku70 and HDAC6. Acetylated Ku70 does not bind to DSB sites, leading to inefficient DNA repair and does not interact with Bax as well, resulting in apoptotic translocation of Bax to mitochondria