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

J. Biol. Chem., Vol. 282, Issue 28, 20256-20263, July 13, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/28/20256    most recent M702366200v1 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 Wood, A. Articles by Burgers, P. M. J. Search for Related Content PubMed PubMed Citation Articles by Wood, A. Articles by Burgers, P. M. J. Social Bookmarking                      What's this?

A Ubiquitin-binding Motif in the Translesion DNA Polymerase Rev1 Mediates Its Essential Functional Interaction with Ubiquitinated Proliferating Cell Nuclear Antigen in Response to DNA Damage^*

From the Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110

During normal DNA replication, the proliferating cell nuclear antigen (PCNA) enhances the processivity of DNA polymerases at the replication fork. When DNA damage is encountered, PCNA is monoubiquitinated on Lys-164 by the Rad6–Rad18 complex as the initiating step of translesion synthesis. DNA damage bypass by the translesion synthesis polymerase Rev1 is enhanced by the presence of ubiquitinated PCNA. Here we have carried out a mutational analysis of Rev1, and we have identified the functional domain in the C terminus of Rev1 that mediates interactions with PCNA. We show that a unique motif within this domain binds the ubiquitin moiety of ubiquitinated PCNA. Point mutations within this ubiquitin-binding motif of Rev1 (L821A,P822A,I825A) abolish its functional interaction with ubiquitinated PCNA in vitro and strongly attenuate damage-induced mutagenesis in vivo. Taken together, these studies suggest a specific mechanism by which the interaction between Rev1 and ubiquitinated PCNA is stabilized during the DNA damage response.

Received for publication, March 20, 2007 , and in revised form, May 4, 2007.

^* This work was supported in part by Grant GM032431 from the National Institutes of Health. 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.

¹ Present address: Genentech, South San Francisco, CA 94080.

² To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Tel.: 314-362-3872; E-mail: burgers{at}biochem.wustl.edu.

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

This article has been cited by other articles:

				J. G. Jansen, A. Tsaalbi-Shtylik, G. Hendriks, H. Gali, A. Hendel, F. Johansson, K. Erixon, Z. Livneh, L. H. F. Mullenders, L. Haracska, et al. Separate Domains of Rev1 Mediate Two Modes of DNA Damage Bypass in Mammalian Cells Mol. Cell. Biol., June 1, 2009; 29(11): 3113 - 3123. [Abstract] [Full Text] [PDF]

				L. S. Waters, B. K. Minesinger, M. E. Wiltrout, S. D'Souza, R. V. Woodruff, and G. C. Walker Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance Microbiol. Mol. Biol. Rev., March 1, 2009; 73(1): 134 - 154. [Abstract] [Full Text] [PDF]

				Y. Wei, J. Jiang, D. Liu, J. Zhou, X. Chen, S. Zhang, H. Zong, X. Yun, and J. Gu Cdc34-mediated Degradation of ATF5 Is Blocked by Cisplatin J. Biol. Chem., July 4, 2008; 283(27): 18773 - 18781. [Abstract] [Full Text] [PDF]

				Z. Zhuang, R. E. Johnson, L. Haracska, L. Prakash, S. Prakash, and S. J. Benkovic Regulation of polymerase exchange between Pol{eta} and Pol{delta} by monoubiquitination of PCNA and the movement of DNA polymerase holoenzyme PNAS, April 8, 2008; 105(14): 5361 - 5366. [Abstract] [Full Text] [PDF]

				S. Takahashi, A. N. Sakamoto, A. Tanaka, and K. Shimizu AtREV1, a Y-Family DNA Polymerase in Arabidopsis, Has Deoxynucleotidyl Transferase Activity in Vitro Plant Physiology, November 1, 2007; 145(3): 1052 - 1060. [Abstract] [Full Text] [PDF]