Three Different Pathways Prevent Chromosome Segregation in the Presence of DNA Damage or Replication Stress in Budding Yeast

PLoS Genetics
Gloria PalouDavid G Quintana

Abstract

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 M-CDK 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.

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Citations

Sep 30, 2016·G3 : Genes - Genomes - Genetics·Nicole A NajorGeorge S Brush
Aug 9, 2019·The EMBO Journal·Michael Charles LanzMarcus Bustamante Smolka
Jun 28, 2020·Journal of Cell Science·Shoily KhondkerAmy E. Ikui
Feb 22, 2017·Cellular and Molecular Life Sciences : CMLS·Michele Giannattasio, Dana Branzei
Aug 5, 2016·Current Genetics·Roger PalouDavid G Quintana
Aug 5, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ze ZhangFanli Zeng
Mar 24, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ping RenFanli Zeng
May 3, 2021·The Journal of Biological Chemistry·Andrew R YoblinskiRaghuvar Dronamraju
Oct 21, 2021·Molecular Biology of the Cell·Cory HaluskaYanchang Wang

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Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
Electrophoresis

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