| First Author | Ma Y | Year | 2026 |
| Journal | Cell Death Dis | Volume | 17 |
| Issue | 1 | Pages | 201 |
| PubMed ID | 41633992 | Mgi Jnum | J:379684 |
| Mgi Id | MGI:8289632 | Doi | 10.1038/s41419-026-08433-6 |
| Citation | Ma Y, et al. (2026) LAP2alpha drives breast tumorigenesis by mitigating replication stress. Cell Death Dis 17(1):201 |
| abstractText | Replication protein A (RPA) plays a vital role in replication stress response, with RPA-coated single-stranded DNA (ssDNA) acting as a critical platform for the coordination of the genome surveillance machinery. In previous studies, we reported that the lamin-associated protein LAP2alpha interacts physically with RPA, aiding its localization to damaged chromatin for genome protection. However, the significance of the LAP2alpha-mediated RPA deposition in tumor progression remains unclear. Here, we reveal that LAP2alpha promotes breast tumorigenesis by counteracting replication stress-induced DNA damage. Furthermore, we demonstrate that defects in RPA loading caused by LAP2alpha deficiency slow breast tumor growth and sensitize tumors to chemotherapeutic treatments. In addition, we found that LAP2alpha could directly stimulate the loading of RPA onto ssDNA. Collectively, our study characterizes a critical role of LAP2alpha-enhanced RPA loading in promoting breast tumorigenesis and positions the LAP2alpha-RPA complex as a promising target for therapeutic intervention in breast cancer. |
