A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication.

Dalia Gritenaite, Lissa N Princz, Barnabas Szakal, Susanne C S Bantele, Lina Wendeler, Sandra Schilbach, Bianca H Habermann, Joao Matos, Michael Lisby, Dana Branzei, Boris Pfander

Genes & development 2014 Jul 15

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A key function of the cellular DNA damage response is to facilitate the bypass of replication fork-stalling DNA lesions. Template switch reactions allow such a bypass and involve the formation of DNA joint molecules (JMs) between sister chromatids. These JMs need to be resolved before cell division; however, the regulation of this process is only poorly understood. Here, we identify a regulatory mechanism in yeast that critically controls JM resolution by the Mus81-Mms4 endonuclease. Central to this regulation is a conserved complex comprising the scaffold proteins Dpb11 and Slx4 that is under stringent control. Cell cycle-dependent phosphorylation of Slx4 by Cdk1 promotes the Dpb11-Slx4 interaction, while in mitosis, phosphorylation of Mms4 by Polo-like kinase Cdc5 promotes the additional association of Mus81-Mms4 with the complex, thereby promoting JM resolution. Finally, the DNA damage checkpoint counteracts Mus81-Mms4 binding to the Dpb11-Slx4 complex. Thus, Dpb11-Slx4 integrates several cellular inputs and participates in the temporal program for activation of the JM-resolving nuclease Mus81. © 2014 Gritenaite et al.; Published by Cold Spring Harbor Laboratory Press.

Citation

Dalia Gritenaite, Lissa N Princz, Barnabas Szakal, Susanne C S Bantele, Lina Wendeler, Sandra Schilbach, Bianca H Habermann, Joao Matos, Michael Lisby, Dana Branzei, Boris Pfander. A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication. Genes & development. 2014 Jul 15;28(14):1604-19