CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair

CtIP is involved in the resection of broken DNA during the S and G2 phases of the cell cycle for repair by recombination. Acting with the MRN complex, it plays a particularly important role in handling complex DNA end structures by localised nucleolytic processing of DNA termini in preparation for l...

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Autores: Wilkinson, Oliver J., Martín-González, Alejandro, Kang, Haejoo, Northall, Sarah J., Wigley, Dale B., Moreno-Herrero, Fernando, Dillingham, Mark Simon
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/174349
Acceso en línea:http://hdl.handle.net/10261/174349
Access Level:acceso abierto
Palabra clave:Chromosomes
Gene expression
Molecular biophysics
Structural biology
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spelling CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repairWilkinson, Oliver J.Martín-González, AlejandroKang, HaejooNorthall, Sarah J.Wigley, Dale B.Moreno-Herrero, FernandoDillingham, Mark SimonChromosomesGene expressionMolecular biophysicsStructural biologyCtIP is involved in the resection of broken DNA during the S and G2 phases of the cell cycle for repair by recombination. Acting with the MRN complex, it plays a particularly important role in handling complex DNA end structures by localised nucleolytic processing of DNA termini in preparation for longer range resection. Here we show that human CtIP is a tetrameric protein adopting a dumbbell architecture in which DNA binding domains are connected by long coiled-coils. The protein complex binds two short DNA duplexes with high affinity and bridges DNA molecules in trans. DNA binding is potentiated by dephosphorylation and is not specific for DNA end structures per se. However, the affinity for linear DNA molecules is increased if the DNA terminates with complex structures including forked ssDNA overhangs and nucleoprotein conjugates. This work provides a biochemical and structural basis for the function of CtIP at complex DNA breaks.Ministerio de Ciencia, Innovación y Universidades (España)European CommissionMinisterio de Economía y Competitividad (España)Peer reviewedeLife Sciences PublicationsConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/174349reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/681299http://dx.doi.org/10.7554/eLife.42129Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1743492026-05-22T06:33:51Z
dc.title.none.fl_str_mv CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
title CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
spellingShingle CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
Wilkinson, Oliver J.
Chromosomes
Gene expression
Molecular biophysics
Structural biology
title_short CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
title_full CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
title_fullStr CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
title_full_unstemmed CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
title_sort CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
dc.creator.none.fl_str_mv Wilkinson, Oliver J.
Martín-González, Alejandro
Kang, Haejoo
Northall, Sarah J.
Wigley, Dale B.
Moreno-Herrero, Fernando
Dillingham, Mark Simon
author Wilkinson, Oliver J.
author_facet Wilkinson, Oliver J.
Martín-González, Alejandro
Kang, Haejoo
Northall, Sarah J.
Wigley, Dale B.
Moreno-Herrero, Fernando
Dillingham, Mark Simon
author_role author
author2 Martín-González, Alejandro
Kang, Haejoo
Northall, Sarah J.
Wigley, Dale B.
Moreno-Herrero, Fernando
Dillingham, Mark Simon
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Chromosomes
Gene expression
Molecular biophysics
Structural biology
topic Chromosomes
Gene expression
Molecular biophysics
Structural biology
description CtIP is involved in the resection of broken DNA during the S and G2 phases of the cell cycle for repair by recombination. Acting with the MRN complex, it plays a particularly important role in handling complex DNA end structures by localised nucleolytic processing of DNA termini in preparation for longer range resection. Here we show that human CtIP is a tetrameric protein adopting a dumbbell architecture in which DNA binding domains are connected by long coiled-coils. The protein complex binds two short DNA duplexes with high affinity and bridges DNA molecules in trans. DNA binding is potentiated by dephosphorylation and is not specific for DNA end structures per se. However, the affinity for linear DNA molecules is increased if the DNA terminates with complex structures including forked ssDNA overhangs and nucleoprotein conjugates. This work provides a biochemical and structural basis for the function of CtIP at complex DNA breaks.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/174349
url http://hdl.handle.net/10261/174349
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/H2020/681299
http://dx.doi.org/10.7554/eLife.42129
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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