PMID: 8598285Mar 1, 1996Paper

Rum1 and Cdc18 link inhibition of cyclin-dependent kinase to the initiation of DNA replication in Schizosaccharomyces pombe

Genes & Development
P V Jallepalli, T J Kelly

Abstract

Eukaryotic cells have evolved regulatory mechanisms to ensure the strict alternation of DNA replication and mitosis. Recent work has suggested that the mitotic form of cyclin-dependent kinase (Cdc2/cyclin B) has a role in preventing re-replication of the genome before mitosis, but the relevant targets of this inhibition are unknown. In this report we present evidence that the mitotic cyclin-dependent kinase affects DNA replication by inhibiting the accumulation and function of Cdc18, a critical regulator of S-phase entry. We found that the ruml+ gene efficiently suppresses the lethality of a conditional cdc18 mutant. Conversely, deletion of ruml+ increases the severity of the cdc18 mutant phenotype, resulting in inappropriate cell division and a rapid loss of viability. Biochemical experiments indicate that Ruml potently inhibits Cdc2 phosphorylation of histone H1 or a Cdc18 fusion protein by directly interacting with the Cdc2/cyclin B complex. Overexpression of Ruml under conditions that promote re-replication of the genome induces a striking accumulation of Cdc18 protein by a largely post-transcriptional mechanism. Overexpression of SIC1, an unrelated cyclin-dependent kinase inhibitor from budding yeast, causes a similar accu...Continue Reading

References

Jan 1, 1991·Annual Review of Cell Biology·S L Forsburg, P Nurse
Jan 1, 1991·Methods in Enzymology·S MorenoP Nurse
May 4, 1990·Cell·C F Lehner, P H O'Farrell
Jul 28, 1989·Cell·S MorenoP Nurse
May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Jun 16, 1995·Cell·T T SuP H O'Farrell
Nov 18, 1994·Cell·R W KingM W Kirschner
Jan 1, 1993·Molecular Biology of the Cell·L Connell-CrowleyJ W Harper

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Citations

Aug 26, 1999·Trends in Genetics : TIG·S L Forsburg
Dec 1, 1996·Current Opinion in Cell Biology·S Chevalier, J J Blow
Jun 1, 1997·Current Opinion in Cell Biology·P V Jallepalli, T J Kelly
Jan 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kara E SawarynskiGeorge S Brush
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·M Botchan
Feb 21, 2002·Molecular Biology of the Cell·Karola LindnerStephen E Kearsey
Oct 8, 1999·Molecular Biology of the Cell·S ElsasserJ L Campbell
Mar 14, 1998·Molecular Biology of the Cell·A Lopez-GironaP Russell
Mar 31, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·B NovakJ J Tyson
Dec 3, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·T TodaK Kominami
Jan 22, 2013·Cold Spring Harbor Perspectives in Biology·Tarek AbbasAnindya Dutta
Nov 14, 1997·Genes & Development·P V JallepalliT J Kelly
Dec 26, 2001·The Plant Cell·M M CastellanoC Gutierrez
Mar 10, 2004·Microbiology and Molecular Biology Reviews : MMBR·Susan L Forsburg
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Dutta, S P Bell
Jan 1, 1997·Annual Review of Microbiology·W M TooneL H Johnston
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·W Jiang, T Hunter
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·V GopalakrishnanT J Kelly
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·G W BrownT J Kelly
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·P V JallepalliT J Kelly
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·Z YanR S Williams
Jan 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jeanette Gowen CookJoseph R Nevins
Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·R S WilliamsB Stillman
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·M WeinreichB Stillman
Apr 1, 1997·Current Opinion in Genetics & Development·A Rowles, J J Blow
Dec 18, 2004·Mutation Research·Sandeep Saxena, Anindya Dutta
Aug 31, 2000·Annual Review of Biochemistry·T J Kelly, G W Brown
Apr 9, 2002·Current Biology : CB·Eishi NoguchiPaul Russell
Feb 23, 2008·Current Biology : CB·Mark L McCleland, Patrick H O'Farrell
Apr 30, 2003·Molecular Cell·Cyrus VaziriAnindya Dutta
Nov 14, 1997·Mayo Clinic Proceedings·B A BarretteP C Roche

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