Subnuclear Relocalization of Structure-Specific Endonucleases in Response to DNA Damage

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Irene Saugar, Alberto Jiménez-Martín, José Antonio Tercero
Structure-specific endonucleases contribute to the maintenance of genome integrity by cleaving DNA intermediates that need to be resolved for faithful DNA repair, replication, or recombination. Despite advances in the understanding of their function and regulation, it is less clear how these proteins respond to genotoxic stress. Here, we show that the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci following DNA damage and colocalizes with the endonucleases Rad1-Rad10 (XPF-ERCC1) and Slx1-Slx4. Recruitment takes place into a class of stress foci defined by Cmr1/WDR76, a protein involved in preserving genome stability, and depends on the E2-ubiquitin-conjugating enzyme Rad6 and the E3-ubiquitin ligase Bre1. Foci dynamics show that, in the presence of DNA intermediates that need resolution by Mus81-Mms4, Mus81 foci persist until this endonuclease is activated by Mms4 phosphorylation. Our data suggest that subnuclear relocalization is relevant for the function of Mus81-Mms4 and, probably, of the endonucleases that colocalize with it.

Graphical abstract

Teaser

Saugar et al. find that, under conditions of DNA damage, the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci, where it colocalizes with the endonucleases Rad1-Rad10 and Slx1-Slx4. Relocalization takes place to a class of stress-induced foci defined by the Cmr1 protein and correlates with the function of the endonuclease.


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