The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart.

Full 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.

Author information

Author/s: Ciccia, Alberto (A); Bredemeyer, Andrea L (AL); Sowa, Mathew E (ME); Terret, Marie-Emilie (ME); Jallepalli, Prasad V (PV); Harper, J Wade (JW); Elledge, Stephen J (SJ);

Affiliation: Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Grants: (Agency:Howard Hughes Medical Institute)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Genes & development (Genes Dev), published in United States. (Language: eng)

Reference: 2009-Oct; vol 23 (issue 20) : pp 2415-25

Dates: Created 2009/10/16; Completed 2009/11/03;

PMID: 19793862, status: MEDLINE (last retrieval date: 11/3/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Genes Dev. 2009 Oct 15;23(20):2359-65. (PMID: 19833762)

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