QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 10, 5026-5039, October 2005

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E05-05-0412v1 16/10/5026    most recent Alert me when this article is cited Alert me if a correction is posted Services 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 Liku, M. E. Articles by Li, J. J. Search for Related Content PubMed PubMed Citation Articles by Liku, M. E. Articles by Li, J. J.

CDK Phosphorylation of a Novel NLS-NES Module Distributed between Two Subunits of the Mcm2-7 Complex Prevents Chromosomal Rereplication

Muluye E. Liku ^*, Van Q. Nguyen , Audrey W. Rosales ^*, Kaoru Irie , and Joachim J. Li 

^* Departments of Biochemistry and Immunology, University of California, San Francisco, CA 94143-2200; Departments of Microbiology and Immunology, University of California, San Francisco, CA 94143-2200

Submitted May 12, 2005; Revised July 26, 2005; Accepted August 2, 2005
Monitoring Editor: Karsten Weis

Cyclin-dependent kinases (CDKs) use multiple mechanisms to block reassembly of prereplicative complexes (pre-RCs) at replication origins to prevent inappropriate rereplication. In Saccharomyces cerevisiae, one of these mechanisms promotes the net nuclear export of a pre-RC component, the Mcm2-7 complex, during S, G2, and M phases. Here we identify two partial nuclear localization signals (NLSs) on Mcm2 and Mcm3 that are each necessary, but not sufficient, for nuclear localization of the Mcm2-7 complex. When brought together in cis, however, the two partial signals constitute a potent NLS, sufficient for robust nuclear localization when fused to an otherwise cytoplasmic protein. We also identify a Crm1-dependent nuclear export signal (NES) adjacent to the Mcm3 NLS. Remarkably, the Mcm2-Mcm3 NLS and the Mcm3 NES are sufficient to form a transport module that recapitulates the cell cycle-regulated localization of the entire Mcm2-7 complex. Moreover, we show that CDK regulation promotes net export by phosphorylation of the Mcm3 portion of this module and that nuclear export of the Mcm2-7 complex is sufficient to disrupt replication initiation. We speculate that the distribution of partial transport signals among distinct subunits of a complex may enhance the specificity of protein localization and raises the possibility that previously undetected distributed transport signals are used by other multiprotein complexes.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Joachim J. Li (jli{at}itsa.ucsf.edu).

This article has been cited by other articles:

				M. Sullivan, L. Holt, and D. O. Morgan Cyclin-Specific Control of Ribosomal DNA Segregation Mol. Cell. Biol., September 1, 2008; 28(17): 5328 - 5336. [Abstract] [Full Text] [PDF]

				A. Devault, E. Gueydon, and E. Schwob Interplay between S-Cyclin-dependent Kinase and Dbf4-dependent Kinase in Controlling DNA Replication through Phosphorylation of Yeast Mcm4 N-Terminal Domain Mol. Biol. Cell, May 1, 2008; 19(5): 2267 - 2277. [Abstract] [Full Text] [PDF]

				S. Neimanis, W. Albig, D. Doenecke, and J. Kahle Sequence Elements in Both Subunits of the DNA Fragmentation Factor Are Essential for Its Nuclear Transport J. Biol. Chem., December 7, 2007; 282(49): 35821 - 35830. [Abstract] [Full Text] [PDF]

				A. M. Moses, M. E. Liku, J. J. Li, and R. Durbin Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase consensus sites PNAS, November 6, 2007; 104(45): 17713 - 17718. [Abstract] [Full Text] [PDF]

				K. A. Braun and L. L. Breeden Nascent Transcription of MCM2-7 Is Important for Nuclear Localization of the Minichromosome Maintenance Complex in G1 Mol. Biol. Cell, April 1, 2007; 18(4): 1447 - 1456. [Abstract] [Full Text] [PDF]

				E. E. Arias and J. C. Walter Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells Genes & Dev., March 1, 2007; 21(5): 497 - 518. [Abstract] [Full Text] [PDF]

				A. E. Ikui, V. Archambault, B. J. Drapkin, V. Campbell, and F. R. Cross Cyclin and Cyclin-Dependent Kinase Substrate Requirements for Preventing Rereplication Reveal the Need for Concomitant Activation and Inhibition Genetics, March 1, 2007; 175(3): 1011 - 1022. [Abstract] [Full Text] [PDF]

				B. Fries, J. Heukeshoven, I. Hauber, C. Gruttner, C. Stocking, R. H. Kehlenbach, J. Hauber, and J. Chemnitz Analysis of Nucleocytoplasmic Trafficking of the HuR Ligand APRIL and Its Influence on CD83 Expression J. Biol. Chem., February 16, 2007; 282(7): 4504 - 4515. [Abstract] [Full Text] [PDF]

				X. An, Z. Zhang, K. Yang, and M. Huang Cotransport of the Heterodimeric Small Subunit of the Saccharomyces cerevisiae Ribonucleotide Reductase Between the Nucleus and the Cytoplasm Genetics, May 1, 2006; 173(1): 63 - 73. [Abstract] [Full Text] [PDF]

				B. M. Green, R. J. Morreale, B. Ozaydin, J. L. DeRisi, and J. J. Li Genome-wide Mapping of DNA Synthesis in Saccharomyces cerevisiae Reveals That Mechanisms Preventing Reinitiation of DNA Replication Are Not Redundant Mol. Biol. Cell, May 1, 2006; 17(5): 2401 - 2414. [Abstract] [Full Text] [PDF]

				Z. Zhang, X. An, K. Yang, D. L. Perlstein, L. Hicks, N. Kelleher, J. Stubbe, and M. Huang Nuclear localization of the Saccharomyces cerevisiae ribonucleotide reductase small subunit requires a karyopherin and a WD40 repeat protein PNAS, January 31, 2006; 103(5): 1422 - 1427. [Abstract] [Full Text] [PDF]