Published online 19 May 2006
Article |
Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links
Laboratory of Molecular Gerontology, National Institute on Aging NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA 1 Lawrence Berkeley National Laboratory, Berkeley CA 94720, USA 2 Department of Molecular Genetics and Microbiology, University of Texas at Austin Austin, TX 78712, USA
*To whom correspondence should be addressed. Tel: +1 410 558 8162; Fax: +1 410 558 8157; Email: vbohr{at}nih.gov
Received March 7, 2006. Revised March 29, 2006. Accepted April 25, 2006.
Cells deficient in the Werner syndrome protein (WRN) or BRCA1 are hypersensitive to DNA interstrand cross-links (ICLs), whose repair requires nucleotide excision repair (NER) and homologous recombination (HR). However, the roles of WRN and BRCA1 in the repair of DNA ICLs are not understood and the molecular mechanisms of ICL repair at the processing stage have not yet been established. This study demonstrates that WRN helicase activity, but not exonuclease activity, is required to process DNA ICLs in cells and that WRN cooperates with BRCA1 in the cellular response to DNA ICLs. BRCA1 interacts directly with WRN and stimulates WRN helicase and exonuclease activities in vitro. The interaction between WRN and BRCA1 increases in cells treated with DNA cross-linking agents. WRN binding to BRCA1 was mapped to BRCA1 452–1079 amino acids. The BRCA1/BARD1 complex also associates with WRN in vivo and stimulates WRN helicase activity on forked and Holliday junction substrates. These findings suggest that WRN and BRCA1 act in a coordinated manner to facilitate repair of DNA ICLs.
Present addresses: Patricia L. Opresko, Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15260, USA
Shurong Huang, Department of Pathology, University of Washington, Seattle, WA 98195, USA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Kobbe, S. Blanck, M. Focke, and H. Puchta Biochemical Characterization of AtRECQ3 Reveals Significant Differences Relative to Other RecQ Helicases Plant Physiology, November 1, 2009; 151(3): 1658 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-J. Liu, A. Barchowsky, and P. L. Opresko The Werner Syndrome Protein Functions in Repair of Cr(VI)-Induced Replication-Associated DNA Damage Toxicol. Sci., August 1, 2009; 110(2): 307 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-H. Cheng, D. Muftic, M. Muftuoglu, L. Dawut, C. Morris, T. Helleday, Y. Shiloh, and V. A. Bohr WRN Is Required for ATM Activation and the S-Phase Checkpoint in Response to Interstrand Cross-Link-Induced DNA Double-Strand Breaks Mol. Biol. Cell, September 1, 2008; 19(9): 3923 - 3933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Grillari, H. Katinger, and R. Voglauer Contributions of DNA interstrand cross-links to aging of cells and organisms Nucleic Acids Res., December 14, 2007; (2007) gkm1065v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Brosh Jr and V. A. Bohr Human premature aging, DNA repair and RecQ helicases Nucleic Acids Res., December 3, 2007; 35(22): 7527 - 7544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Hisama, V. A. Bohr, and J. Oshima WRN's Tenth Anniversary Sci. Aging Knowl. Environ., June 28, 2006; 2006(10): pe18 - pe18. [Abstract] [Full Text]
|
|