The annealing helicase HARP protects stalled replication forks.

Full Abstract

Mutations in HepA-related protein (HARP) are the only identified causes of Schimke immunoosseous dysplasia (SIOD). HARP has a unique annealing helicase activity in vitro, but the in vivo functional significance remains unknown. Here, we demonstrated that HARP is recruited to stalled replication forks via its direct interaction with Replication protein A (RPA). Cells with HARP depletion displayed increased spontaneous DNA damage and G2/M arrest, suggesting that HARP normally acts to stabilize stalled replication forks. Our data place the annealing helicase activity of HARP at replication forks and propose that SIOD syndrome may be caused by the destabilization of replication forks during cell proliferation.

Author information

Author/s: Yuan, Jingsong (J); Ghosal, Gargi (G); Chen, Junjie (J);

Affiliation: Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

Journal and publication information

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

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

Reference: 2009-Oct; vol 23 (issue 20) : pp 2394-9

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

PMID: 19793864, 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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