HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 49, 40559-40567, December 9, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/49/40559    most recent M508453200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, N. Articles by Legerski, R. J. Search for Related Content PubMed PubMed Citation Articles by Zhang, N. Articles by Legerski, R. J. Social Bookmarking                      What's this?

The Pso4 mRNA Splicing and DNA Repair Complex Interacts with WRN for Processing of DNA Interstrand Cross-links^*

Nianxiang Zhang, Ramandeep Kaur, Xiaoyan Lu, Xi Shen, Lei Li, and Randy J. Legerski1

From the Departments of Molecular Genetics and Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

DNA interstrand cross-links (ICLs) are perhaps the most formidable lesion encountered by the cellular DNA repair machinery, and the elucidation of the process by which they are removed in eukaryotic cells has proved a daunting task. In particular, the early stages of adduct recognition and uncoupling of the cross-link have remained elusive principally because genetic studies have not been highly revealing. We have developed a biochemical assay in which processing of a DNA substrate containing a site-specific psoralen ICL can be monitored in vitro. Using this assay we have shown previously that the mismatch repair factor MutS, the nucleotide excision repair heterodimer Ercc1-Xpf, and the replication proteins RPA and PCNA are involved in an early stage of psoralen ICL processing. Here, we report the identification of two additional factors required in the ICL repair process, a previously characterized pre-mRNA splicing complex composed of Pso4/Prp19, Cdc5L, Plrg1, and Spf27 (Pso4 complex), and WRN the protein deficient in Werner syndrome. Analysis of the WRN protein indicates that its DNA helicase function, but not its exonuclease activity, is required for ICL processing in vitro. In addition, we show that WRN and the Pso4 complex interact through a direct physical association between WRN and Cdc5L. A putative model for uncoupling of ICLs in mammalian cells is presented.

Received for publication, August 2, 2005 , and in revised form, October 12, 2005.

^* This work was supported by NCI/National Institutes of Health Grants CA075160, CA097175, and CA09102. DNA sequencing resources were supported by the Cancer Center Support (Core) Grant CA16672. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S3 and supplemental Ref. 1.

¹ To whom correspondence should be addressed: Dept. of Molecular Genetics, University of Texas M. D. Anderson Cancer, 1515 Holcombe Blvd., Houston, TX 77030. Tel.: 713-834-6363; Fax. 713-834-6319; E-mail: rlegersk{at}mdanderson.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. D. Beck, S.-J. Park, Y.-J. Lee, Y. Roman, R. A. Hromas, and S.-H. Lee Human Pso4 Is a Metnase (SETMAR)-binding Partner That Regulates Metnase Function in DNA Repair J. Biol. Chem., April 4, 2008; 283(14): 9023 - 9030. [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]

				N. Saydam, R. Kanagaraj, T. Dietschy, P. L. Garcia, J. Pena-Diaz, I. Shevelev, I. Stagljar, and P. Janscak Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors Nucleic Acids Res., September 27, 2007; 35(17): 5706 - 5716. [Abstract] [Full Text] [PDF]

				K. Palma, Q. Zhao, Y. T. Cheng, D. Bi, J. Monaghan, W. Cheng, Y. Zhang, and X. Li Regulation of plant innate immunity by three proteins in a complex conserved across the plant and animal kingdoms Genes & Dev., June 15, 2007; 21(12): 1484 - 1493. [Abstract] [Full Text] [PDF]

				K. Fortschegger, B. Wagner, R. Voglauer, H. Katinger, M. Sibilia, and J. Grillari Early Embryonic Lethality of Mice Lacking the Essential Protein SNEV Mol. Cell. Biol., April 15, 2007; 27(8): 3123 - 3130. [Abstract] [Full Text] [PDF]

				A. S. Multani and S. Chang WRN at telomeres: implications for aging and cancer J. Cell Sci., March 1, 2007; 120(5): 713 - 721. [Abstract] [Full Text] [PDF]

				M. Otterlei, P. Bruheim, B. Ahn, W. Bussen, P. Karmakar, K. Baynton, and V. A. Bohr Werner syndrome protein participates in a complex with RAD51, RAD54, RAD54B and ATR in response to ICL-induced replication arrest J. Cell Sci., December 15, 2006; 119(24): 5137 - 5146. [Abstract] [Full Text] [PDF]