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

J. Biol. Chem., Vol. 282, Issue 44, 31937-31943, November 2, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/44/31937    most recent M704554200v1 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 Wu, P.-Y. Articles by Calsou, P. Search for Related Content PubMed PubMed Citation Articles by Wu, P.-Y. Articles by Calsou, P. Social Bookmarking                      What's this?

Interplay between Cernunnos-XLF and Nonhomologous End-joining Proteins at DNA Ends in the Cell^*

Peï-Yu Wu, Philippe Frit, Laurent Malivert^¶, Patrick Revy^¶, Denis Biard^||, Bernard Salles¹, and Patrick Calsou²

From the Institut de Pharmacologie et de Biologie Structurale, CNRS-Université de Toulouse, UMR 5089, 205 route de Narbonne, 31077 Toulouse, Cedex 4, France, INSERM, Hôpital Necker-Enfants Malades, U768, UnitéDéveloppement Normal et Pathologique du Système Immunitaire, F-75015 Paris, France, ^¶Université Paris Descartes, Faculté de Médecine René Descartes, F-75005 Paris, France, and ^||Commissariat à l'Energie Atomique, Laboratoire de Génétique de la Radiosensibilité, Institut de Radiobiologie Cellulaire et Moléculaire, Direction des Sciences du Vivant, BP6, 92265 Fontenay-aux-Roses, France

Cernunnos-XLF is the most recently identified core component in the nonhomologous end-joining (NHEJ) pathway for the repair of DNA double strand breaks (DSBs) in mammals. It associates with the XRCC4/ligase IV ligation complex and stimulates its activity in a still unknown manner. NHEJ also requires the DNA-dependent protein kinase that contains a Ku70/Ku80 heterodimer and the DNA-dependent protein kinase catalytic subunit. To understand the interplay between Cernunnos-XLF and the other proteins implicated in the NHEJ process, we have analyzed the interactions of Cernunnos-XLF and NHEJ proteins in cells after treatment with DNA double strand-breaking agents by means of a detergent-based cellular fractionation protocol. We report that Cernunnos-XLF is corecruited with the core NHEJ components on chromatin damaged with DSBs in human cells and is phosphorylated by the DNA-dependent protein kinase catalytic subunit. Our data show a pivotal role for DNA ligase IV in the NHEJ ligation complex assembly and recruitment to DSBs because the association of Cernunnos-XLF with the XRCC4/ligase IV complex relies primarily on the DNA ligase IV component, and an intact XRCC4/ligase IV complex is necessary for Cernunnos-XLF mobilization to damaged chromatin. Conversely, a Cernunnos-XLF defect has no apparent impact on the XRCC4/ligase IV association and recruitment to the DSBs or on the stimulation of the DNA-dependent protein kinase on DNA ends.

Received for publication, June 4, 2007 , and in revised form, August 21, 2007.

^* This work was supported in part by grants from the Association pour la Recherche sur le Cancer, the Ligue Nationale Contre le Cancer ("équipe labelisée"), the Commisariat à l'Energie Atomique, and a radiobiology grant from Electricité de France. 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 "Materials and Methods" and supplemental Figs. 1–5.

² Supported by INSERM.

¹ To whom correspondence should be addressed. Tel.: 33-5-61-17-59-36; Fax: 33-5-61-17-59-33; E-mail: bernard.salles{at}ipbs.fr.

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

This article has been cited by other articles:

				P.-Y. Wu, P. Frit, S. Meesala, S. Dauvillier, M. Modesti, S. N. Andres, Y. Huang, J. Sekiguchi, P. Calsou, B. Salles, et al. Structural and Functional Interaction between the Human DNA Repair Proteins DNA Ligase IV and XRCC4 Mol. Cell. Biol., June 1, 2009; 29(11): 3163 - 3172. [Abstract] [Full Text] [PDF]

				L. Malivert, I. Callebaut, P. Rivera-Munoz, A. Fischer, J.-P. Mornon, P. Revy, and J.-P. de Villartay The C-Terminal Domain of Cernunnos/XLF Is Dispensable for DNA Repair In Vivo Mol. Cell. Biol., March 1, 2009; 29(5): 1116 - 1122. [Abstract] [Full Text] [PDF]

				E. Riballo, L. Woodbine, T. Stiff, S. A. Walker, A. A. Goodarzi, and P. A. Jeggo XLF-Cernunnos promotes DNA ligase IV-XRCC4 re-adenylation following ligation Nucleic Acids Res., February 1, 2009; 37(2): 482 - 492. [Abstract] [Full Text] [PDF]

				S. Jayaram, G. Ketner, N. Adachi, and L. A. Hanakahi Loss of DNA ligase IV prevents recognition of DNA by double-strand break repair proteins XRCC4 and XLF Nucleic Acids Res., October 1, 2008; 36(18): 5773 - 5786. [Abstract] [Full Text] [PDF]

				D. Wu, L. M. Topper, and T. E. Wilson Recruitment and Dissociation of Nonhomologous End Joining Proteins at a DNA Double-Strand Break in Saccharomyces cerevisiae Genetics, March 1, 2008; 178(3): 1237 - 1249. [Abstract] [Full Text] [PDF]