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

J. Biol. Chem., Vol. 282, Issue 32, 23184-23193, August 10, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/32/23184    most recent M701042200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bish, R. A. Articles by Myers, M. P. Search for Related Content PubMed PubMed Citation Articles by Bish, R. A. Articles by Myers, M. P. Social Bookmarking                      What's this?

Werner Helicase-interacting Protein 1 Binds Polyubiquitin via Its Zinc Finger Domain^*

From the Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724

DNA repair is regulated on many levels by ubiquitination. In order to identify novel connections between DNA repair pathways and ubiquitin signaling, we used mass spectrometry to identify proteins that interact with lysine 6-linked polyubiquitin chains. From this proteomic screen, we identified the DNA repair protein WRNIP1 (Werner helicase-interacting protein 1), along with nucleosome assembly protein 1, as novel ubiquitin-interacting proteins. We found that a small zinc finger domain at the N terminus of WRNIP1 is sufficient and necessary for noncovalent ubiquitin binding. This ubiquitin-binding zinc finger (UBZ) domain binds polyubiquitin but not monoubiquitin and appears to show no specificity for polyubiquitin chain linkage. A homologous zinc finger domain in RAD18 also binds polyubiquitin, suggesting a wider role for the UBZ domain in DNA repair. The WRNIP1 ubiquitin-binding function, along with its previously established ATPase activity, suggests that WRNIP1 plays a role in the metabolism of ubiquitinated proteins. Supporting this model, deletion of MGS1, the yeast homolog of WRNIP1, slows the rate of ubiquitin turnover, rendering yeast resistant to cycloheximide. We also find that WRNIP1 is heavily modified with ubiquitin and SUMO, revealing complex layers in the involvement of ubiquitin pathway proteins in the regulation of DNA repair. The novel ubiquitin-binding ability of WRNIP1 sheds light on the role of UBZ domain-containing proteins in postreplication DNA repair.

Received for publication, February 2, 2007 , and in revised form, May 23, 2007.

^* 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 Tables 1–3.

¹ Recipient of a David H. Koch Fellowship of the Watson School of Biological Sciences and a fellowship from the American Foundation for Aging Research and also supported by Grant GM 065094 from the NIGMS, National Institutes of Health.

² Supported by Grants 25603521 and 25102067 from the NCI, National Institutes of Health. To whom correspondence should be addressed: Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, NY 11724. Tel.: 516-367-6806; Fax: 516-367-8873; E-mail: myers{at}cshl.edu.

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

This article has been cited by other articles:

				K. Watanabe, K. Iwabuchi, J. Sun, Y. Tsuji, T. Tani, K. Tokunaga, T. Date, M. Hashimoto, M. Yamaizumi, and S. Tateishi RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1 Nucleic Acids Res., April 1, 2009; 37(7): 2176 - 2193. [Abstract] [Full Text] [PDF]

				N. Crosetto, M. Bienko, R. G. Hibbert, T. Perica, C. Ambrogio, T. Kensche, K. Hofmann, T. K. Sixma, and I. Dikic Human Wrnip1 Is Localized in Replication Factories in a Ubiquitin-binding Zinc Finger-dependent Manner J. Biol. Chem., December 12, 2008; 283(50): 35173 - 35185. [Abstract] [Full Text] [PDF]

				V. Notenboom, R. G. Hibbert, S. E. van Rossum-Fikkert, J. V. Olsen, M. Mann, and T. K. Sixma Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification Nucleic Acids Res., September 27, 2007; 35(17): 5819 - 5830. [Abstract] [Full Text] [PDF]