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

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;...

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Autores principales: Gritenaite, Dalia, Princz, Lissa N., Szakal, Barnabas, Bantele, Susanne C.S., Wendeler, Lina, Schilbach, Sandra, Habermann, Bianca H., Matos, Joao, Lisby, Michael, Branzei, Dana, Pfander, Boris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102767/
https://www.ncbi.nlm.nih.gov/pubmed/25030699
http://dx.doi.org/10.1101/gad.240515.114
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author Gritenaite, Dalia
Princz, Lissa N.
Szakal, Barnabas
Bantele, Susanne C.S.
Wendeler, Lina
Schilbach, Sandra
Habermann, Bianca H.
Matos, Joao
Lisby, Michael
Branzei, Dana
Pfander, Boris
author_facet Gritenaite, Dalia
Princz, Lissa N.
Szakal, Barnabas
Bantele, Susanne C.S.
Wendeler, Lina
Schilbach, Sandra
Habermann, Bianca H.
Matos, Joao
Lisby, Michael
Branzei, Dana
Pfander, Boris
author_sort Gritenaite, Dalia
collection PubMed
description 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.
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spelling pubmed-41027672015-01-15 A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication Gritenaite, Dalia Princz, Lissa N. Szakal, Barnabas Bantele, Susanne C.S. Wendeler, Lina Schilbach, Sandra Habermann, Bianca H. Matos, Joao Lisby, Michael Branzei, Dana Pfander, Boris Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2014-07-15 /pmc/articles/PMC4102767/ /pubmed/25030699 http://dx.doi.org/10.1101/gad.240515.114 Text en © 2014 Gritenaite et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Gritenaite, Dalia
Princz, Lissa N.
Szakal, Barnabas
Bantele, Susanne C.S.
Wendeler, Lina
Schilbach, Sandra
Habermann, Bianca H.
Matos, Joao
Lisby, Michael
Branzei, Dana
Pfander, Boris
A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication
title A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication
title_full A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication
title_fullStr A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication
title_full_unstemmed A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication
title_short A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication
title_sort cell cycle-regulated slx4–dpb11 complex promotes the resolution of dna repair intermediates linked to stalled replication
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102767/
https://www.ncbi.nlm.nih.gov/pubmed/25030699
http://dx.doi.org/10.1101/gad.240515.114
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