Show simple item record

dc.contributor.authorMorales, Carmen
dc.contributor.authorRuiz-Torres, Miguel
dc.contributor.authorRodríguez-Acebes, Sara
dc.contributor.authorRodríguez-Corsino, Miriam
dc.contributor.authorCisneros, David A
dc.contributor.authorPeters, Jan-Michael
dc.contributor.authorLafarga, Vanesa 
dc.contributor.authorMegias Vazquez, Diego 
dc.contributor.authorMendez, Juan 
dc.contributor.authorLosada, Ana
dc.identifier.citationJ Biol Chem. 2020;295(1):146-157.es_ES
dc.description.abstractCohesin is a chromatin-bound complex that mediates sister chromatid cohesion and facilitates long-range interactions through DNA looping. How the transcription and replication machineries deal with the presence of cohesin on chromatin remains unclear. The dynamic association of cohesin with chromatin depends on WAPL cohesin release factor (WAPL) and on PDS5 cohesin-associated factor (PDS5), which exists in two versions in vertebrate cells, PDS5A and PDS5B. Using genetic deletion in mouse embryo fibroblasts and a combination of CRISPR-mediated gene editing and RNAi-mediated gene silencing in human cells, here we analyzed the consequences of PDS5 depletion for DNA replication. We found that either PDS5A or PDS5B is sufficient for proper cohesin dynamics and that their simultaneous removal increases cohesin's residence time on chromatin and slows down DNA replication. A similar phenotype was observed in WAPL-depleted cells. Cohesin down-regulation restored normal replication fork rates in PDS5-deficient cells, suggesting that chromatin-bound cohesin hinders the advance of the replisome. We further show that PDS5 proteins are required to recruit WRN helicase-interacting protein 1 (WRNIP1), RAD51 recombinase (RAD51), and BRCA2 DNA repair associated (BRCA2) to stalled forks and that in their absence, nascent DNA strands at unprotected forks are degraded by MRE11 homolog double-strand break repair nuclease (MRE11). These findings indicate that PDS5 proteins participate in replication fork protection and also provide insights into how cohesin and its regulators contribute to the response to replication stress, a common feature of cancer cells.es_ES
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Economy and Competitiveness and FEDER Grants BFU2013-48481-R and BFU2016-79841-R (to A. L.) and BFU2016-80402-R (to J. M.) and by FPI "Severo Ochoa" fellowships (to C. M. and M. R.-T.). This work was also supported by funding from Boehringer Ingelheim Fonds (to M. R.-T.). The authors declare that they have no conflicts of interest with the contents of this article.es_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biology (ASBMB) es_ES
dc.subject.meshDNA Replication es_ES
dc.subject.meshATPases Associated with Diverse Cellular Activities es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBRCA2 Protein es_ES
dc.subject.meshCell Cycle Proteins es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshChromatin es_ES
dc.subject.meshChromosomal Proteins, Non-Histonees_ES
dc.subject.meshDNA-Binding Proteins es_ES
dc.subject.meshHeLa Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMRE11 Homologue Protein es_ES
dc.subject.meshMice es_ES
dc.subject.meshNuclear Proteins es_ES
dc.subject.meshRad51 Recombinase es_ES
dc.subject.meshTranscription Factors es_ES
dc.titlePDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España) 
dc.contributor.funderUnión Europea. Comisión Europea 
dc.identifier.journalThe Journal of biological chemistryes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Dinámica Cromosómicaes_ES
dc.rights.accessRightsopen accesses_ES

Files in this item

Acceso Abierto
Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional