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Vol. 15, Issue 12, 5443-5455, December 2004

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A Ddc2-Rad53 Fusion Protein Can Bypass the Requirements for RAD9 and MRC1 in Rad53 Activation

Soo-Jung Lee ^*, Jimmy K. Duong , and David F. Stern  

Department of Pathology, Yale University School of Medicine, New Haven, CT 06510; ^* Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94107

Submitted July 20, 2004; Revised September 17, 2004; Accepted September 20, 2004
Monitoring Editor: Douglas Koshland

Activation of Rad53p by DNA damage plays an essential role in DNA damage checkpoint pathways. Rad53p activation requires coupling of Rad53p to Mec1p through a "mediator" protein, Rad9p or Mrc1p. We sought to determine whether the mediator requirement could be circumvented by making fusion proteins between the Mec1 binding partner Ddc2p and Rad53p. Ddc2-Rad53p interacted with Mec1p and other Ddc2-Rad53p molecules under basal conditions and displayed an increased oligomerization upon DNA damage. Ddc2-Rad53p was activated in a Mec1p- and Tel1p-dependent manner upon DNA damage. Expression of Ddc2-Rad53p in rad9 or rad9mrc1 cells increased viability on plates containing the alkylating agent methyl methane sulfonate. Ddc2-Rad53p was activated at least partially by DNA damage in rad9mrc1 cells. In addition, expression of Ddc2-Rad53p in rad24rad17mec3 cells increased cell survival. These results reveal minimal requirements for function of a core checkpoint signaling system.

Corresponding author. E-mail address: df.stern{at}yale.edu.

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