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| Subject Categories: Cell Cycle | Genome Stability & Dynamics |
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| The EMBO Journal
(2006) 25, 1987–1996, doi:10.1038/sj.emboj.7601075 Published online 13 April 2006 |
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| A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2–Dpb11 |
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| Yon-Soo Tak1, 2, 4, Yoshimi Tanaka1, 3, Shizuko Endo1, Yoichiro Kamimura1, 2, 3, 5 and Hiroyuki Araki1, 2, 3 |
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1 Division of Microbial Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Shizuoka, Japan 2 Department of Genetics, SOKENDAI, Mishima, Shizuoka, Japan 3 CREST, Kawaguchi, Saitama, Japan To whom correspondence should be addressed Hiroyuki Araki, Division of Microbial Genetics, National Institute of Genetics, Research Organization of Information and Systems, Yata 1111, Mishima, Shizuoka 411-8540, Japan. Tel.: +81 55 981 6754; Fax: +81 55 981 6762; E-mail: hiaraki@lab.nig.ac.jp 4 Present address: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea 5 Present address: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Received 8 November 2005; Accepted 9 March 2006; Published online 13 April 2006. |
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| Abstract |
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| Phosphorylation often regulates protein–protein interactions to control biological reactions. The Sld2 and Dpb11 proteins of budding yeast form a phosphorylation-dependent complex that is essential for chromosomal DNA replication. The Sld2 protein has a cluster of 11 cyclin-dependent kinase (CDK) phosphorylation motifs (Ser/Thr–Pro), six of which match the canonical sequences Ser/Thr–Pro–X–Lys/Arg, Lys/Arg–Ser/Thr–Pro and Ser/Thr–Pro–Lys/Arg. Simultaneous alanine substitution for serine or threonine in all the canonical CDK-phosphorylation motifs severely reduces complex formation between Sld2 and Dpb11, and inhibits DNA replication. Here we show that phosphorylation of these canonical motifs does not play a direct role in complex formation, but rather regulates phosphorylation of another residue, Thr84. This constitutes a non-canonical CDK-phosphorylation motif within a 28-amino-acid sequence that is responsible, after phosphorylation, for binding of Sld2–Dpb11. We further suggest that CDK-catalysed phosphorylation of sites other than Thr84 renders Thr84 accessible to CDK. Finally, we argue that this novel mechanism sets a threshold of CDK activity for formation of the essential Sld2 to Dpb11 complex and therefore prevents premature DNA replication. |
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| Keywords: BRCT, CDK, DNA replication, phosphorylation, S phase |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHNature Article (18 Jan 2007) CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast Nature Letters to Editor (18 Jan 2007) S-Cdk-dependent phosphorylation of Sld2 essential for chromosomal DNA replication in budding yeast Nature Letters to Editor (07 Feb 2002) Xenopus Cut5 is essential for a CDK-dependent process in the initiation of DNA replication The EMBO Journal Article (15 May 2003) |
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