| First Author | Steger M | Year | 2013 |
| Journal | Mol Cell | Volume | 50 |
| Issue | 3 | Pages | 333-43 |
| PubMed ID | 23623683 | Mgi Jnum | J:203494 |
| Mgi Id | MGI:5527121 | Doi | 10.1016/j.molcel.2013.03.023 |
| Citation | Steger M, et al. (2013) Prolyl isomerase PIN1 regulates DNA double-strand break repair by counteracting DNA end resection. Mol Cell 50(3):333-43 |
| abstractText | The regulation of DNA double-strand break (DSB) repair by phosphorylation-dependent signaling pathways is crucial for the maintenance of genome stability; however, remarkably little is known about the molecular mechanisms by which phosphorylation controls DSB repair. Here, we show that PIN1, a phosphorylation-specific prolyl isomerase, interacts with key DSB repair factors and affects the relative contributions of homologous recombination (HR) and nonhomologous end-joining (NHEJ) to DSB repair. We find that PIN1-deficient cells display reduced NHEJ due to increased DNA end resection, whereas resection and HR are compromised in PIN1-overexpressing cells. Moreover, we identify CtIP as a substrate of PIN1 and show that DSBs become hyperresected in cells expressing a CtIP mutant refractory to PIN1 recognition. Mechanistically, we provide evidence that PIN1 impinges on CtIP stability by promoting its ubiquitylation and subsequent proteasomal degradation. Collectively, these data uncover PIN1-mediated isomerization as a regulatory mechanism coordinating DSB repair. |
