A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions

Summary: DNA repair scaffolds mediate specific DNA and protein interactions in order to assist repair enzymes in recognizing and removing damaged sequences. Many scaffold proteins are dedicated to repairing a particular type of lesion. Here, we show that the budding yeast Saw1 scaffold is more versa...

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Main Authors: Prabha Sarangi, Veronika Altmannova, Cory Holland, Zdenka Bartosova, Fanfan Hao, Dorothea Anrather, Gustav Ammerer, Sang Eun Lee, Lumir Krejci, Xiaolan Zhao
Format: Article
Language:English
Published: Elsevier 2014-10-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221112471400730X
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spelling doaj-f56841cc41524ee68b7396b83e363d1e2020-11-25T01:12:21ZengElsevierCell Reports2211-12472014-10-0191143152A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease InteractionsPrabha Sarangi0Veronika Altmannova1Cory Holland2Zdenka Bartosova3Fanfan Hao4Dorothea Anrather5Gustav Ammerer6Sang Eun Lee7Lumir Krejci8Xiaolan Zhao9Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USADepartment of Biology, Masaryk University, Brno 62500, Czech RepublicDepartment of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USADepartment of Biology, Masaryk University, Brno 62500, Czech RepublicMolecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USADepartment of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, AustriaDepartment of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, AustriaDepartment of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Division of Radiation Biology, Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USADepartment of Biology, Masaryk University, Brno 62500, Czech Republic; National Centre for Biomolecular Research, Masaryk University, Brno 62500, Czech Republic; International Clinical Research Center, St. Anne’s University Hospital in Brno, Brno 60200, Czech Republic; Corresponding authorMolecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Corresponding authorSummary: DNA repair scaffolds mediate specific DNA and protein interactions in order to assist repair enzymes in recognizing and removing damaged sequences. Many scaffold proteins are dedicated to repairing a particular type of lesion. Here, we show that the budding yeast Saw1 scaffold is more versatile. It helps cells cope with base lesions and protein-DNA adducts through its known function of recruiting the Rad1-Rad10 nuclease to DNA. In addition, it promotes UV survival via a mechanism mediated by its sumoylation. Saw1 sumoylation favors its interaction with another nuclease Slx1-Slx4, and this SUMO-mediated role is genetically separable from two main UV lesion repair processes. These effects of Saw1 and its sumoylation suggest that Saw1 is a multifunctional scaffold that can facilitate diverse types of DNA repair through its modification and nuclease interactions. : Scaffold proteins are not DNA repair enzymes themselves but make important contributions to DNA repair by regulating and coordinating various enzymes with their DNA substrates. Sarangi et al. reveal the versatility of the Saw1 scaffold by identifying how it copes with several types of DNA damage that depend on its nuclease interactions and sumoylation. These findings highlight the diverse ways in which multifunctional scaffolds can operate under genotoxic stress and how this is directed by protein modification.http://www.sciencedirect.com/science/article/pii/S221112471400730X
collection DOAJ
language English
format Article
sources DOAJ
author Prabha Sarangi
Veronika Altmannova
Cory Holland
Zdenka Bartosova
Fanfan Hao
Dorothea Anrather
Gustav Ammerer
Sang Eun Lee
Lumir Krejci
Xiaolan Zhao
spellingShingle Prabha Sarangi
Veronika Altmannova
Cory Holland
Zdenka Bartosova
Fanfan Hao
Dorothea Anrather
Gustav Ammerer
Sang Eun Lee
Lumir Krejci
Xiaolan Zhao
A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions
Cell Reports
author_facet Prabha Sarangi
Veronika Altmannova
Cory Holland
Zdenka Bartosova
Fanfan Hao
Dorothea Anrather
Gustav Ammerer
Sang Eun Lee
Lumir Krejci
Xiaolan Zhao
author_sort Prabha Sarangi
title A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions
title_short A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions
title_full A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions
title_fullStr A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions
title_full_unstemmed A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions
title_sort versatile scaffold contributes to damage survival via sumoylation and nuclease interactions
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2014-10-01
description Summary: DNA repair scaffolds mediate specific DNA and protein interactions in order to assist repair enzymes in recognizing and removing damaged sequences. Many scaffold proteins are dedicated to repairing a particular type of lesion. Here, we show that the budding yeast Saw1 scaffold is more versatile. It helps cells cope with base lesions and protein-DNA adducts through its known function of recruiting the Rad1-Rad10 nuclease to DNA. In addition, it promotes UV survival via a mechanism mediated by its sumoylation. Saw1 sumoylation favors its interaction with another nuclease Slx1-Slx4, and this SUMO-mediated role is genetically separable from two main UV lesion repair processes. These effects of Saw1 and its sumoylation suggest that Saw1 is a multifunctional scaffold that can facilitate diverse types of DNA repair through its modification and nuclease interactions. : Scaffold proteins are not DNA repair enzymes themselves but make important contributions to DNA repair by regulating and coordinating various enzymes with their DNA substrates. Sarangi et al. reveal the versatility of the Saw1 scaffold by identifying how it copes with several types of DNA damage that depend on its nuclease interactions and sumoylation. These findings highlight the diverse ways in which multifunctional scaffolds can operate under genotoxic stress and how this is directed by protein modification.
url http://www.sciencedirect.com/science/article/pii/S221112471400730X
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