The similarities between essential molecular mechanisms in Archaea and Eukarya make it possible to discover, using comparative genomics, new fundamental mechanisms conserved between these two domains. We are studying a complex of two proteins conserved in Archaea and Eukarya whose precise biological role and biochemical function remain unknown. One of them is a universal protein known as Kae1 (kinase-asociated endopeptidase 1). The second protein is a serine/threonine kinase corresponding to the proteins Bud32 in Saccharomyces cerevisiae and PRPK (p53-related protein kinase) in humans. The genes encoding the archaeal orthologues of Kae1 and PRPK are either contiguous or even fused in many archaeal genomes. In S. cerevisiae, Kae1 and Bud32 (PRPK) belong to a chromatin-associated complex [KEOPS (kinase, endopeptidase and other proteins of small size)/EKC (endopeptidase-like kinase chromatin-associated)] that is essential for telomere elongation and transcription of essential genes. Although Kae1 is annotated as O-sialoglycoprotein endopeptidase in most genomes, we found that the Kae1 protein from Pyrococcus abyssi has no protease activity, but is an atypical DNA-binding protein with an AP (apurinic) lyase activity. The structure of the fusion protein from Methanocaldococcus jannaschii revealed that Kae1 maintains the ATP-binding site of Kae1 in an inactive configuration. We have in fact found that Kae1 inhibits the kinase activity of Bud32 (PRPK) in vitro. Understanding the precise biochemical function and biological role of these two proteins (which are probably essential for genome maintenance) remains a major challenge.
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February 2009
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Conference Article|
January 20 2009
The universal Kae1 protein and the associated Bud32 kinase (PRPK), a mysterious protein couple probably essential for genome maintenance in Archaea and Eukarya
Arnaud Hecker;
Arnaud Hecker
*Université Paris-Sud, Institut de Génétique et Microbiologie, IFR115, UMR8621-CNRS, 91405 Orsay Cedex, France
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Marc Graille;
Marc Graille
†Université Paris-Sud, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, IFR115, UMR8619-CNRS, 91405 Orsay, France
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Edwige Madec;
Edwige Madec
*Université Paris-Sud, Institut de Génétique et Microbiologie, IFR115, UMR8621-CNRS, 91405 Orsay Cedex, France
‡Université des Sciences et Technologies de Lille, Laboratoire de Génétique des Enveloppes Bactériennes, CNRS UMR 8576, 59655 Villeneuve d'Ascq, France
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Danièle Gadelle;
Danièle Gadelle
*Université Paris-Sud, Institut de Génétique et Microbiologie, IFR115, UMR8621-CNRS, 91405 Orsay Cedex, France
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Eric Le Cam;
Eric Le Cam
§Université Paris-Sud, Institut Gustave Roussy, Interactions Moléculaires et Cancer, UMR8126-CNRS, 94805 Villejuif Cedex, France
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Herman van Tilbergh;
Herman van Tilbergh
†Université Paris-Sud, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, IFR115, UMR8619-CNRS, 91405 Orsay, France
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Patrick Forterre
Patrick Forterre
1
*Université Paris-Sud, Institut de Génétique et Microbiologie, IFR115, UMR8621-CNRS, 91405 Orsay Cedex, France
1To whom correspondence should be addressed (email patrick.forterre@igmors.u-psud.fr).
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Publisher: Portland Press Ltd
Received:
September 30 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem Soc Trans (2009) 37 (1): 29–35.
Article history
Received:
September 30 2008
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Arnaud Hecker, Marc Graille, Edwige Madec, Danièle Gadelle, Eric Le Cam, Herman van Tilbergh, Patrick Forterre; The universal Kae1 protein and the associated Bud32 kinase (PRPK), a mysterious protein couple probably essential for genome maintenance in Archaea and Eukarya. Biochem Soc Trans 1 February 2009; 37 (1): 29–35. doi: https://doi.org/10.1042/BST0370029
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