Mec1 [ATR (ataxia telangiectasia mutated- and Rad3-related) in humans] is the principle kinase responsible for checkpoint activation in response to replication stress and DNA damage in Saccharomyces cerevisiae. The heterotrimeric checkpoint clamp, 9-1-1 (checkpoint clamp of Rad9, Rad1 and Hus1 in humans and Ddc1, Rad17 and Mec3 in S. cerevisiae; Ddc1-Mec3-Rad17) and the DNA replication initiation factor Dpb11 (human TopBP1) are the two known activators of Mec1. The 9-1-1 clamp functions in checkpoint activation in G1- and G2-phase, but its employment differs between these two phases of the cell cycle. The Ddc1 (human Rad9) subunit of the clamp directly activates Mec1 in G1-phase, an activity identified only in S. cerevisiae so far. However, in G2-phase, the 9-1-1 clamp activates the checkpoint by two mechanisms. One mechanism includes direct activation of Mec1 by the unstructured C-terminal tail of Ddc1. The second mech-anism involves the recruitment of Dpb11 by the phosphorylated C-terminal tail of Ddc1. The latter mechanism is highly conserved and also functions in response to replication stress in higher eukaryotes. In S. cerevisiae, however, both the 9-1-1 clamp and the Dpb11 are partially redundant for checkpoint activation in response to replication stress, suggesting the existence of additional activators of Mec1.
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Conference Article|
March 22 2011
Cell-cycle-specific activators of the Mec1/ATR checkpoint kinase
Vasundhara M. Navadgi-Patil;
Vasundhara M. Navadgi-Patil
1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, U.S.A.
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Peter M. Burgers
Peter M. Burgers
1
1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, U.S.A.
1To whom correspondence should be addressed (email burgers@biochem.wustl.edu).
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Publisher: Portland Press Ltd
Received:
September 15 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (2): 600–605.
Article history
Received:
September 15 2010
Citation
Vasundhara M. Navadgi-Patil, Peter M. Burgers; Cell-cycle-specific activators of the Mec1/ATR checkpoint kinase. Biochem Soc Trans 1 April 2011; 39 (2): 600–605. doi: https://doi.org/10.1042/BST0390600
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