The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart Journal Article
| Authors: | Ciccia, A.; Bredemeyer, A. L.; Sowa, M. E.; Terret, M. E.; Jallepalli, P. V.; Harper, J. W.; Elledge, S. J. |
| Article Title: | The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart |
| Abstract: | The 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. © 2009 by Cold Spring Harbor Laboratory Press. |
| Keywords: | controlled study; unclassified drug; human cell; dna replication; mitosis; dna damage; cell cycle s phase; embryo; protein; protein interaction; fibroblast; cell cycle arrest; replication factor a; dna double-strand breaks; dna replication stress; harp; smarcal1 protein; dna replication origin; genetic disorder; schimke immunoosseous dysplasia |
| Journal Title: | Genes and Development |
| Volume: | 23 |
| Issue: | 20 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2009-10-15 |
| Start Page: | 2415 |
| End Page: | 2425 |
| Language: | English |
| DOI: | 10.1101/gad.1832309 |
| PROVIDER: | scopus |
| PMCID: | PMC2764500 |
| PUBMED: | 19793862 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 30 November 2010" - "CODEN: GEDEE" - "Source: Scopus" |
