Ciccia, AlbertoBredemeyer, Andrea L.Sowa, Mathew E.Terret, Marie-EmilieJallepalli, Prasad V.Harper, J. WadeElledge, Stephen J.2019-10-122009Ciccia, A., A. L. Bredemeyer, M. E. Sowa, M.-E. Terret, P. V. Jallepalli, J. W. Harper, and S. J. Elledge. 2009. “The SIOD Disorder Protein SMARCAL1 Is an RPA-Interacting Protein Involved in Replication Fork Restart.” Genes & Development23 (20): 2415–25. doi:10.1101/gad.1832309.0890-93691549-5477http://nrs.harvard.edu/urn-3:HUL.InstRepos:41542690The integrity of genomic DNA is continuously challenged by the presence of DNA base lesions or DNA strand breaks. Here we report the identification of a new DNA damage response protein, SMARCAL1 (SWI/SNF-related, matrix associated, actin-dependent regulator of chromatin, subfamily a-like 1), which is a member of the SNF2 family and is mutated in Schimke immunoosseous dysplasia (SIOD). We demonstrate that SMARCAL1 directly interacts with Replication protein A (RPA) and is recruited to sites of DNA damage in an RPA-dependent manner. SMARCAL1-depleted cells display sensitivity to DNA-damaging agents that induce replication fork collapse, and exhibit slower fork recovery and delayed entry into mitosis following S-phase arrest. Furthermore, SIOD patient fibroblasts reconstituted with SMARCAL1 exhibit faster cell cycle progression after S-phase arrest. Thus, the symptoms of SIOD may be caused, at least in part, by defects in the cellular response to DNA replication stress.en-USJournal Article2019-10-1210.1101/gad.1832309