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G3 (Bethesda). 2014 Apr 2;4(6):1059-69. doi: 10.1534/g3.114.011205.

Conditional genetic interactions of RTT107, SLX4, and HRQ1 reveal dynamic networks upon DNA damage in S. cerevisiae.

Author information

1
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, B.C. Canada V5Z 4H4.
2
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, California 94158.
3
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, B.C. Canada V5Z 4H4 msk@cmmt.ubc.ca.

Abstract

The DNA damage response (DDR) is a dynamic process that is crucial for protecting the cell from challenges to genome integrity. Although many genome-wide studies in Saccharomyces cerevisiae have identified genes that contribute to resistance to DNA-damaging agents, more work is needed to elucidate the changes in genetic interaction networks in response to DNA lesions. Here we used conditional epistatic miniarray profiling to analyze the genetic interaction networks of the DDR genes RTT107, SLX4, and HRQ1 under three DNA-damaging conditions: camptothecin, hydroxyurea, and methyl methanesulfonate. Rtt107 and its interaction partner Slx4 are targets of the checkpoint kinase Mec1, which is central to the DDR-signaling cascades. Hrq1 recently was identified as a novel member of the RecQ helicase family in S. cerevisiae but is still poorly characterized. The conditional genetic networks that we generated revealed functional insights into all three genes and showed that there were varied responses to different DNA damaging agents. We observed that RTT107 had more genetic interactions under camptothecin conditions than SLX4 or HRQ1, suggesting that Rtt107 has an important role in response to this type of DNA lesion. Although RTT107 and SLX4 function together, they also had many distinct genetic interactions. In particular, RTT107 and SLX4 showed contrasting genetic interactions for a few genes, which we validated with independently constructed strains. Interestingly, HRQ1 had a genetic interaction profile that correlated with that of SLX4 and both were enriched for very similar gene ontology terms, suggesting that they function together in the DDR.

KEYWORDS:

DNA damage response; conditional interactions; genetic interaction profiles; helicase

PMID:
24700328
PMCID:
PMC4065249
DOI:
10.1534/g3.114.011205
[Indexed for MEDLINE]
Free PMC Article
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