Dbf4‐dependent kinase and the Rtt107 scaffold promote Mus81‐Mms4 resolvase activation during mitosis
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Date
2017-01-17
Publication Type
Journal Article
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yes
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Abstract
DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81‐Mms4, this cell cycle stage‐specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7‐Dbf4 (DDK), targets Mus81‐Mms4 in conjunction with Cdc5—both kinases bind to as well as phosphorylate Mus81‐Mms4 in an interdependent manner. Moreover, DDK‐mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis, establishing DDK as a novel regulator of homologous recombination. The scaffold protein Rtt107, which binds the Mus81‐Mms4 complex, interacts with Cdc7 and thereby targets DDK and Cdc5 to the complex enabling full Mus81 activation. Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK. Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution.
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published
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Book title
Journal / series
Volume
36 (5)
Pages / Article No.
664 - 678
Publisher
Wiley
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Edition / version
Methods
Software
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Date collected
Date created
Subject
Cell cycle; Genome stability; Homologous recombination; Joint molecule resolution; Post-translational modification
Organisational unit
09457 - Matos, Joao (ehemalig) / Matos, Joao (former)
Notes
Funding
153058 - Coordination of DNA repair and segregation during meiosis and mitosis (SNF)
155823 - Rewiring the DNA repair machinery for genome stability and haploidisation (SNF)
155823 - Rewiring the DNA repair machinery for genome stability and haploidisation (SNF)