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Reference - PMID:16371652 - Production of reactive oxygen species in response to replication stress and inappropriate mitosis in fission yeast.

Reference summary

PubMed ID
PMID:16371652
Title
Production of reactive oxygen species in response to replication stress and inappropriate mitosis in fission yeast.
Authors
Marchetti MA, Weinberger M, Murakami Y, Burhans WC, Huberman JA
Citation
J Cell Sci 2006 Jan 01;119(Pt 1):124-31
Publication year
2006
Abstract
Previous studies have indicated that replication stress can trigger apoptosis-like cell death, accompanied (where tested) by production of reactive oxygen species (ROS), in mammalian cells and budding yeast (Saccharomyces cerevisiae). In mammalian cells, inappropriate entry into mitosis also leads to cell death. Here, we report similar responses in fission yeast (Schizosaccharomyces pombe). We used ROS- and death-specific fluorescent stains to measure the effects of mutations in replication initiation and checkpoint genes in fission yeast on the frequencies of ROS production and cell death. We found that certain mutant alleles of each of the four tested replication initiation genes caused elevated ROS and cell death. Where tested, these effects were not enhanced by checkpoint-gene mutations. Instead, when cells competent for replication but defective in both the replication and damage checkpoints were treated with hydroxyurea, which slows replication fork movement, the frequencies of ROS production and cell death were greatly increased. This was a consequence of elevated CDK activity, which permitted inappropriate entry into mitosis. Thus, studies in fission yeast are likely to prove helpful in understanding the pathways that lead from replication stress and inappropriate mitosis to cell death in mammalian cells.

Annotation

Multi-locus phenotype

FYPO:0003004 - increased cellular reactive oxygen species level during vegetative growth

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FYPO:0003118 - normal cellular reactive oxygen species level during vegetative growth

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Single locus phenotype

FYPO:0000400 - abnormal cell cycle arrest at mitotic G2/M phase transition

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FYPO:0000611 - abnormal cell cycle arrest in mitotic S phase

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FYPO:0003004 - increased cellular reactive oxygen species level during vegetative growth

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FYPO:0000377 - increased frequency of apoptosis

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FYPO:0000378 - normal apoptosis

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Genotypes:

FYPO:0003118 - normal cellular reactive oxygen species level during vegetative growth

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