Three Different Pathways Prevent Chromosome Segregation in the Presence of DNA Damage or Replication Stress in Budding Yeast
Palou Marin, Gloria (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Palou, Roger (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Zeng, Fanli (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Vashisht, Ajay A. (University of California. Department of Biological Chemistry)
Wohlschlegel, James A. (University of California. Department of Biological Chemistry)
Garcia Quintana, David (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2015
Resum:	A surveillance mechanism, the S phase checkpoint, blocks progression into mitosis in response to DNA damage and replication stress. Segregation of damaged or incompletely replicated chromosomes results in genomic instability. In humans, the S phase checkpoint has been shown to constitute an anti-cancer barrier. Inhibition of mitotic cyclin dependent kinase (M-CDK) activity by Wee1 kinases is critical to block mitosis in some organisms. However, such mechanism is dispensable in the response to genotoxic stress in the model eukaryotic organism Saccharomyces cerevisiae. We show here that the Wee1 ortholog Swe1 does indeed inhibit M-CDK activity and chromosome segregation in response to genotoxic insults. Swe1 dispensability in budding yeast is the result of a redundant control of MCDK activity by the checkpoint kinase Rad53. In addition, our results indicate that Swe1 is an effector of the checkpoint central kinase Mec1. When checkpoint control on M-CDK and on Pds1/securin stabilization are abrogated, cells undergo aberrant chromosome segregation.
Ajuts:	Ministerio de Economía y Competitividad BFU2011-28007
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PLOS genetics, Vol. 11, Issue 9 (September 2015) , art. e1005468, ISSN 1553-7404

DOI: 10.1371/journal.pgen.1005468
PMID: 26332045

22 p, 4.3 MB

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