The annealing helicase HARP protects stalled replication forks
- Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
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.
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Footnotes
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↵1 Corresponding author.
E-MAIL jchen8{at}mdanderson.org; FAX (713) 745-6141.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1836409.
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Supplemental material is available at http://www.genesdev.org.
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- Received June 25, 2009.
- Accepted August 20, 2009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press
