This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chiolo, I.
Right arrow Articles by Liberi, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chiolo, I.
Right arrow Articles by Liberi, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2005, p. 5738-5751, Vol. 25, No. 13
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.13.5738-5751.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Srs2 and Sgs1 DNA Helicases Associate with Mre11 in Different Subcomplexes following Checkpoint Activation and CDK1-Mediated Srs2 Phosphorylation{dagger}

Irene Chiolo,1 Walter Carotenuto,1 Giulio Maffioletti,1,{ddagger} John H. J. Petrini,2 Marco Foiani,1 and Giordano Liberi1*

FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy, and Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy,1 Molecular Biology Program, Memorial Sloan Kettering Cancer Center, and Cornell University Graduate School of Medical Sciences, 1275 York Avenue, New York, New York 100212

Received 25 January 2005/ Returned for modification 24 February 2005/ Accepted 31 March 2005

Mutations in the genes encoding the BLM and WRN RecQ DNA helicases and the MRE11-RAD50-NBS1 complex lead to genome instability and cancer predisposition syndromes. The Saccharomyces cerevisiae Sgs1 RecQ helicase and the Mre11 protein, together with the Srs2 DNA helicase, prevent chromosome rearrangements and are implicated in the DNA damage checkpoint response and in DNA recombination. By searching for Srs2 physical interactors, we have identified Sgs1 and Mre11. We show that Srs2, Sgs1, and Mre11 form a large complex, likely together with yet unidentified proteins. This complex reorganizes into Srs2-Mre11 and Sgs1-Mre11 subcomplexes following DNA damage-induced activation of the Mec1 and Tel1 checkpoint kinases. The defects in subcomplex formation observed in mec1 and tel1 cells can be recapitulated in srs2-7AV mutants that are hypersensitive to intra-S DNA damage and are altered in the DNA damage-induced and Cdk1-dependent phosphorylation of Srs2. Altogether our observations indicate that Mec1- and Tel1-dependent checkpoint pathways modulate the functional interactions between Srs2, Sgs1, and Mre11 and that the Srs2 DNA helicase represents an important target of the Cdk1-mediated cellular response induced by DNA damage.

* Corresponding author. Mailing address: FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy. Phone: +39-02-574303-529. Fax: +39-02-574303-310. E-mail:giordano.liberi{at}ifom-ieo-campus.it.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: University of Dundee, Dow Street, Dundee, DD1 5EH, United Kingdom.

Molecular and Cellular Biology, July 2005, p. 5738-5751, Vol. 25, No. 13
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.13.5738-5751.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Colavito, S., Macris-Kiss, M., Seong, C., Gleeson, O., Greene, E. C., Klein, H. L., Krejci, L., Sung, P. (2009). Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption. Nucleic Acids Res 0: gkp748v1-gkp748 [Abstract] [Full Text]  
  • Carter, S. D., Vigasova, D., Chen, J., Chovanec, M., Astrom, S. U. (2009). Nej1 recruits the Srs2 helicase to DNA double-strand breaks and supports repair by a single-strand annealing-like mechanism. Proc. Natl. Acad. Sci. USA 106: 12037-12042 [Abstract] [Full Text]  
  • Zheng, L., Kanagaraj, R., Mihaljevic, B., Schwendener, S., Sartori, A. A., Gerrits, B., Shevelev, I., Janscak, P. (2009). MRE11 complex links RECQ5 helicase to sites of DNA damage. Nucleic Acids Res 37: 2645-2657 [Abstract] [Full Text]  
  • Sollier, J., Driscoll, R., Castellucci, F., Foiani, M., Jackson, S. P., Branzei, D. (2009). The Saccharomyces cerevisiae Esc2 and Smc5-6 Proteins Promote Sister Chromatid Junction-mediated Intra-S Repair. Mol. Biol. Cell 20: 1671-1682 [Abstract] [Full Text]  
  • Chiolo, I., Saponaro, M., Baryshnikova, A., Kim, J.-H., Seo, Y.-S., Liberi, G. (2007). The Human F-Box DNA Helicase FBH1 Faces Saccharomyces cerevisiae Srs2 and Postreplication Repair Pathway Roles. Mol. Cell. Biol. 27: 7439-7450 [Abstract] [Full Text]  
  • Zlatanova, J., Seebart, C., Tomschik, M. (2007). Nap1: taking a closer look at a juggler protein of extraordinary skills. FASEB J. 21: 1294-1310 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»