Search for mutants of the helicase MCM defective in DNA damage tolerance

DNA damage compromises genome integrity and can lead to cell death. Cells have evolved a variety of processes to respond to DNA damage including the DNA damage tolerance (DDT) response. DDT pathways promote the bypass of blocking lesions by DNA polymerases during DNA replication, and the subsequent...

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Detalles Bibliográficos
Autor: González Garrido, Cristina
Tipo de recurso: tesis de maestría
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/180649
Acceso en línea:http://hdl.handle.net/10261/180649
Access Level:acceso abierto
Palabra clave:DNA damage tolerance
MCM
Replication
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spelling Search for mutants of the helicase MCM defective in DNA damage toleranceGonzález Garrido, CristinaDNA damage toleranceMCMReplicationDNA damage compromises genome integrity and can lead to cell death. Cells have evolved a variety of processes to respond to DNA damage including the DNA damage tolerance (DDT) response. DDT pathways promote the bypass of blocking lesions by DNA polymerases during DNA replication, and the subsequent filling of the ssDNA left behind the fork. Two distinct DDT mechanisms have been characterized. One is translesion synthesis (TLS), which uses specialized TLS polymerases that have the ability to replicate across DNA lesions. The other is the error-free template switching (TS) mechanism, which uses homologous recombination (HR) proteins to bypass the damage and filling the ssDNA gaps using the sister chromatid as a template. The binding of HR proteins to the damage is coupled to the replication process during DDT. A potential candidate to promote this binding is the replicative helicase MCM, which interacts physically with the homologous recombination proteins Rad51 and Rad52. In this work, we have searched for MMS sensitive mutants of MCM subunits to demonstrate the implication of MCM in DDT. In addition, we have analyzed the putative role of Mcm4-T355 in DDT. We have found that both mutations in Mcm2 and the replacement of Mcm4-T355 by either a phosphomimetic or a phosphomutant residue cause sensitivity to methyl methane sulfonate (MMS), connecting genetically the helicase MCM with the DDT response.Peer reviewedCSIC-JA-UPO-USE - Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)Universidad de SevillaPrado, FélixConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192018info:eu-repo/semantics/masterThesishttp://purl.org/coar/resource_type/c_bdcchttp://hdl.handle.net/10261/180649reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1806492026-05-22T06:33:51Z
dc.title.none.fl_str_mv Search for mutants of the helicase MCM defective in DNA damage tolerance
title Search for mutants of the helicase MCM defective in DNA damage tolerance
spellingShingle Search for mutants of the helicase MCM defective in DNA damage tolerance
González Garrido, Cristina
DNA damage tolerance
MCM
Replication
title_short Search for mutants of the helicase MCM defective in DNA damage tolerance
title_full Search for mutants of the helicase MCM defective in DNA damage tolerance
title_fullStr Search for mutants of the helicase MCM defective in DNA damage tolerance
title_full_unstemmed Search for mutants of the helicase MCM defective in DNA damage tolerance
title_sort Search for mutants of the helicase MCM defective in DNA damage tolerance
dc.creator.none.fl_str_mv González Garrido, Cristina
author González Garrido, Cristina
author_facet González Garrido, Cristina
author_role author
dc.contributor.none.fl_str_mv Prado, Félix
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv DNA damage tolerance
MCM
Replication
topic DNA damage tolerance
MCM
Replication
description DNA damage compromises genome integrity and can lead to cell death. Cells have evolved a variety of processes to respond to DNA damage including the DNA damage tolerance (DDT) response. DDT pathways promote the bypass of blocking lesions by DNA polymerases during DNA replication, and the subsequent filling of the ssDNA left behind the fork. Two distinct DDT mechanisms have been characterized. One is translesion synthesis (TLS), which uses specialized TLS polymerases that have the ability to replicate across DNA lesions. The other is the error-free template switching (TS) mechanism, which uses homologous recombination (HR) proteins to bypass the damage and filling the ssDNA gaps using the sister chromatid as a template. The binding of HR proteins to the damage is coupled to the replication process during DDT. A potential candidate to promote this binding is the replicative helicase MCM, which interacts physically with the homologous recombination proteins Rad51 and Rad52. In this work, we have searched for MMS sensitive mutants of MCM subunits to demonstrate the implication of MCM in DDT. In addition, we have analyzed the putative role of Mcm4-T355 in DDT. We have found that both mutations in Mcm2 and the replacement of Mcm4-T355 by either a phosphomimetic or a phosphomutant residue cause sensitivity to methyl methane sulfonate (MMS), connecting genetically the helicase MCM with the DDT response.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/masterThesis
http://purl.org/coar/resource_type/c_bdcc
format masterThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/180649
url http://hdl.handle.net/10261/180649
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv CSIC-JA-UPO-USE - Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)
Universidad de Sevilla
publisher.none.fl_str_mv CSIC-JA-UPO-USE - Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)
Universidad de Sevilla
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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