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FHA domain mediated protein interaction network of Dun1 identifies its novel functions in the DNA damage response
Author(s) -
Chen Shenghong,
Smolka Marcus B,
Zhou Huilin
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a509
Subject(s) - dna damage , microbiology and biotechnology , biology , dna replication , g2 m dna damage checkpoint , replication protein a , dna repair , eukaryotic dna replication , sumo protein , seqa protein domain , dna , dna binding protein , genetics , cell cycle checkpoint , gene , cell cycle , ubiquitin , transcription factor
The DNA damage checkpoint kinase Dun1 is crucial for the transduction of DNA damage signal to regulate downstream processes in the budding yeast Saccharomyces cerevisiae. To uncover the function of Dun1 in the DNA damage response, we carried out a proteomic screening of proteins that bind specifically to its Forkhead‐associated (FHA) domain, a known modular protein interaction domain. Multiple functional groups of proteins have been identified as specific binding proteins of the Dun1 FHA domain. Among them, Rad9 and Mrc1, two adaptor proteins in the DNA damage checkpoint pathways, were found to interact directly with the FHA domain of Dun1 following DNA damage treatment. Such interaction is likely important for Dun1 activation and its targeting to the sites of DNA damage and DNA replication fork in vivo. Interestingly, a number of proteins involved in cell cycle regulation, gene silencing, chromosome segregation and others are also found as specific binding proteins of the Dun1 FHA domain. Among them, a group of proteins implicated in protein trafficking and regulation of actin polymerization were found, including Sec2, Ede1, Rgd1, Osh2, Bbc1, Bzz1 and others. Deletion analysis of these genes showed that they are involved in the response to DNA replication stress. Finally, we show that various dun1 mutants exhibit defects in actin depolymerization and morphogenesis in response to DNA replication stress. Thus, we conclude that the FHA domain of Dun1 is responsible for the targeting of Dun1 to coordinate DNA damage induced global cellular responses.