The tumour suppressor PTEN antagonizes PI3K signalling in the cytoplasm. PTEN can also be found in the nucleus, where its function is unclear. Bassi et al. have shown that sumoylation of PTEN promotes nuclear localization, and genotoxic stress (ionizing radiation (IR)) leads to decreased levels of nuclear PTEN. Nuclear PTEN was required for the repair of DNA double-strand breaks, and lack of sumoylated PTEN increased the sensitivity of cells to IR. Furthermore PTEN−/− xenograft tumours were sensitive to the combination of a genotoxic agent (cisplatin or IR) and a PI3K inhibitor, thus this combination may have therapeutic potential against PTEN-null tumours.