A role for the spindle assembly checkpoint in the DNA damage response

Spontaneous DNA damage poses a continuous threat to genomic integrity. If unchecked, genotoxic insults result in genomic instability, a hallmark of cancer cells. In eukaryotic cells a DNA Damage Response (DDR) detects and responds to genotoxic stress, acting as an anti-cancer barrier in humans. Amon...

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Authors: Palou, Roger|||0000-0001-7674-9358, Palou Marin, Gloria|||0000-0002-1077-4275, Garcia Quintana, David|||0000-0002-4909-6686
Format: article
Publication Date:2016
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:185943
Online Access:https://ddd.uab.cat/record/185943
https://dx.doi.org/urn:doi:10.1007/s00294-016-0634-y
Access Level:Open access
Keyword:DNA damage response (DDR)
Spindle assembly checkpoint (SAC)
S Phase checkpoint
Chromosome segregation
Genomic instability
Cyclin Dependent Kinase (Cdk1)
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spelling A role for the spindle assembly checkpoint in the DNA damage responsePalou, Roger|||0000-0001-7674-9358Palou Marin, Gloria|||0000-0002-1077-4275Garcia Quintana, David|||0000-0002-4909-6686DNA damage response (DDR)Spindle assembly checkpoint (SAC)S Phase checkpointChromosome segregationGenomic instabilityCyclin Dependent Kinase (Cdk1)Spontaneous DNA damage poses a continuous threat to genomic integrity. If unchecked, genotoxic insults result in genomic instability, a hallmark of cancer cells. In eukaryotic cells a DNA Damage Response (DDR) detects and responds to genotoxic stress, acting as an anti-cancer barrier in humans. Among other actions, the DDR blocks the segregation of incompletely replicated or damaged chromosomes, thus preventing aneuploidy. In a work aimed at better understanding such S-M control, we recently showed that cells block anaphase through different control pathways. The S phase checkpoint kinase Mec1/ATR inhibits mitotic Cyclin Dependent Kinase activity through effector kinases Swe1/Wee1 and Rad53/Chk2. Cells also stabilize the levels of Pds1/securin to block sister chromatid segregation in response to DNA damage. We show here that Pds1/securin abundance is still secured when the S phase checkpoint response is fully abrogated in mec1/ATR tel1/ATM double null mutants. When such cells are exposed to genotoxic stress, Pds1/securin is stabilized in a spindle assembly checkpoint (SAC) dependent manner. Disruption of the SAC and the S phase checkpoint together, allows chromosome segregation in the presence of DNA damage or replication stress. Our results place the SAC as a part of the DDR, which appears to count on different, independent control layers to preserve genomic integrity when chromosome replication is challenged. 22016-01-0120162016-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/185943https://dx.doi.org/urn:doi:10.1007/s00294-016-0634-yreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2011/28007Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2015/68493-Popen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1859432026-06-06T12:50:31Z
dc.title.none.fl_str_mv A role for the spindle assembly checkpoint in the DNA damage response
title A role for the spindle assembly checkpoint in the DNA damage response
spellingShingle A role for the spindle assembly checkpoint in the DNA damage response
Palou, Roger|||0000-0001-7674-9358
DNA damage response (DDR)
Spindle assembly checkpoint (SAC)
S Phase checkpoint
Chromosome segregation
Genomic instability
Cyclin Dependent Kinase (Cdk1)
title_short A role for the spindle assembly checkpoint in the DNA damage response
title_full A role for the spindle assembly checkpoint in the DNA damage response
title_fullStr A role for the spindle assembly checkpoint in the DNA damage response
title_full_unstemmed A role for the spindle assembly checkpoint in the DNA damage response
title_sort A role for the spindle assembly checkpoint in the DNA damage response
dc.creator.none.fl_str_mv Palou, Roger|||0000-0001-7674-9358
Palou Marin, Gloria|||0000-0002-1077-4275
Garcia Quintana, David|||0000-0002-4909-6686
author Palou, Roger|||0000-0001-7674-9358
author_facet Palou, Roger|||0000-0001-7674-9358
Palou Marin, Gloria|||0000-0002-1077-4275
Garcia Quintana, David|||0000-0002-4909-6686
author_role author
author2 Palou Marin, Gloria|||0000-0002-1077-4275
Garcia Quintana, David|||0000-0002-4909-6686
author2_role author
author
dc.subject.none.fl_str_mv DNA damage response (DDR)
Spindle assembly checkpoint (SAC)
S Phase checkpoint
Chromosome segregation
Genomic instability
Cyclin Dependent Kinase (Cdk1)
topic DNA damage response (DDR)
Spindle assembly checkpoint (SAC)
S Phase checkpoint
Chromosome segregation
Genomic instability
Cyclin Dependent Kinase (Cdk1)
description Spontaneous DNA damage poses a continuous threat to genomic integrity. If unchecked, genotoxic insults result in genomic instability, a hallmark of cancer cells. In eukaryotic cells a DNA Damage Response (DDR) detects and responds to genotoxic stress, acting as an anti-cancer barrier in humans. Among other actions, the DDR blocks the segregation of incompletely replicated or damaged chromosomes, thus preventing aneuploidy. In a work aimed at better understanding such S-M control, we recently showed that cells block anaphase through different control pathways. The S phase checkpoint kinase Mec1/ATR inhibits mitotic Cyclin Dependent Kinase activity through effector kinases Swe1/Wee1 and Rad53/Chk2. Cells also stabilize the levels of Pds1/securin to block sister chromatid segregation in response to DNA damage. We show here that Pds1/securin abundance is still secured when the S phase checkpoint response is fully abrogated in mec1/ATR tel1/ATM double null mutants. When such cells are exposed to genotoxic stress, Pds1/securin is stabilized in a spindle assembly checkpoint (SAC) dependent manner. Disruption of the SAC and the S phase checkpoint together, allows chromosome segregation in the presence of DNA damage or replication stress. Our results place the SAC as a part of the DDR, which appears to count on different, independent control layers to preserve genomic integrity when chromosome replication is challenged.
publishDate 2016
dc.date.none.fl_str_mv 2
2016-01-01
2016
2016-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/185943
https://dx.doi.org/urn:doi:10.1007/s00294-016-0634-y
url https://ddd.uab.cat/record/185943
https://dx.doi.org/urn:doi:10.1007/s00294-016-0634-y
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2011/28007
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2015/68493-P
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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