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Mol Biol Cell. 2004 Dec;15(12):5443-55. Epub 2004 Sep 29.

A Ddc2-Rad53 fusion protein can bypass the requirements for RAD9 and MRC1 in Rad53 activation.

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Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.


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 Deltarad9 or Deltarad9Deltamrc1 cells increased viability on plates containing the alkylating agent methyl methane sulfonate. Ddc2-Rad53p was activated at least partially by DNA damage in Deltarad9Deltamrc1 cells. In addition, expression of Ddc2-Rad53p in Deltarad24Deltarad17Deltamec3 cells increased cell survival. These results reveal minimal requirements for function of a core checkpoint signaling system.

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