Nonsense-mediated decay regulates key components of homologous recombination

Ryan Janke, Jeremy Kong, Hannes Braberg, Greg Cantin, John R. Yates, Nevan J. Krogan, Wolf Dietrich Heyer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cells frequently experience DNA damage that requires repair by homologous recombination (HR). Proteins involved in HR are carefully coordinated to ensure proper and efficient repair without interfering with normal cellular processes. In Saccharomyces cerevisiae, Rad55 functions in the early steps of HR and is regulated in response to DNA damage through phosphorylation by the Mec1 and Rad53 kinases of the DNA damage response. To further identify regulatory processes that target HR, we performed a high-throughput genetic interaction screen with RAD55 phosphorylation site mutants. Genes involved in the mRNA quality control process, nonsense-mediated decay (NMD), were found to genetically interact with rad55 phospho-site mutants. Further characterization revealed that RAD55 transcript and protein levels are regulated by NMD. Regulation of HR by NMD extends to multiple targets beyond RAD55, including RAD51, RAD54 and RAD57. Finally, we demonstrate that loss of NMD results in an increase in recombination rates and resistance to the DNA damaging agent methyl methanesulfonate, suggesting this pathway negatively regulates HR under normal growth conditions.

Original languageEnglish (US)
Pages (from-to)5218-5230
Number of pages13
JournalNucleic Acids Research
Volume44
Issue number11
DOIs
StatePublished - Jun 20 2016

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Homologous Recombination
DNA Damage
Phosphorylation
Methyl Methanesulfonate
Recombinational DNA Repair
Quality Control
Genetic Recombination
Saccharomyces cerevisiae
Proteins
Phosphotransferases
Messenger RNA
DNA
Growth
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Janke, R., Kong, J., Braberg, H., Cantin, G., Yates, J. R., Krogan, N. J., & Heyer, W. D. (2016). Nonsense-mediated decay regulates key components of homologous recombination. Nucleic Acids Research, 44(11), 5218-5230. https://doi.org/10.1093/nar/gkw182

Nonsense-mediated decay regulates key components of homologous recombination. / Janke, Ryan; Kong, Jeremy; Braberg, Hannes; Cantin, Greg; Yates, John R.; Krogan, Nevan J.; Heyer, Wolf Dietrich.

In: Nucleic Acids Research, Vol. 44, No. 11, 20.06.2016, p. 5218-5230.

Research output: Contribution to journalArticle

Janke, R, Kong, J, Braberg, H, Cantin, G, Yates, JR, Krogan, NJ & Heyer, WD 2016, 'Nonsense-mediated decay regulates key components of homologous recombination', Nucleic Acids Research, vol. 44, no. 11, pp. 5218-5230. https://doi.org/10.1093/nar/gkw182
Janke R, Kong J, Braberg H, Cantin G, Yates JR, Krogan NJ et al. Nonsense-mediated decay regulates key components of homologous recombination. Nucleic Acids Research. 2016 Jun 20;44(11):5218-5230. https://doi.org/10.1093/nar/gkw182
Janke, Ryan ; Kong, Jeremy ; Braberg, Hannes ; Cantin, Greg ; Yates, John R. ; Krogan, Nevan J. ; Heyer, Wolf Dietrich. / Nonsense-mediated decay regulates key components of homologous recombination. In: Nucleic Acids Research. 2016 ; Vol. 44, No. 11. pp. 5218-5230.
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