Basis for the Checkpoint Signal Specificity That Regulates Chk1 and Cds1 Protein Kinases

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Published inMolecular and Cellular Biology Vol. 19; no. 6; pp. 4262 - 4269
Main Authors Brondello, Jean-Marc, Boddy, Michael N., Furnari, Beth, Russell, Paul
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.06.1999
Taylor & Francis
Subjects
Cell Cycle - physiology
Cell Growth and Development
Cell Nucleus - metabolism
Checkpoint Kinase 1
Checkpoint Kinase 2
DNA Repair - physiology
Enzyme Inhibitors - pharmacology
GTP-Binding Proteins - physiology
Hydroxyurea - pharmacology
Immunoblotting
Phosphorylation
Protein Kinases - physiology
Protein-Serine-Threonine Kinases
ras Proteins
Recombinant Fusion Proteins
S Phase - physiology
Schizosaccharomyces - physiology
Schizosaccharomyces pombe
Schizosaccharomyces pombe Proteins
Time Factors
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Abstract Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
AbstractList Six checkpoint Rad proteins (Rad1, Rad3, Rad9, Rad17, Rad26, and Hus1) are needed to regulate checkpoint protein kinases Chk1 and Cds1 in fission yeast. Chk1 is required to prevent mitosis when DNA is damaged by ionizing radiation (IR), whereas either kinase is sufficient to prevent mitosis when DNA replication is inhibited by hydroxyurea (HU). Checkpoint Rad proteins are required for IR-induced phosphorylation of Chk1 and HU-induced activation of Cds1. IR activates Cds1 only during the DNA synthesis (S) phase, whereas HU induces Chk1 phosphorylation only in cds1 mutants. Here, we investigate the basis of the checkpoint signal specificity of Chk1 phosphorylation and Cds1 activation. We show that IR fails to induce Chk1 phosphorylation in HU-arrested cells. Release from the HU arrest following IR causes substantial Chk1 phosphorylation. These and other data indicate that Cds1 prevents Chk1 phosphorylation in HU-arrested cells, which suggests that Cds1 actively suppresses a repair process that leads to Chk1 phosphorylation. Cds1 becomes more highly concentrated in the nucleus only during the S phase of the cell cycle. This finding correlates with S-phase specificity of IR-induced activation of Cds1. However, constitutive nuclear localization of Cds1 does not enhance IR-induced activation of Cds1. This result suggests that Cds1 activation requires DNA structures or protein activities that are present only during S phase. These findings help to explain how Chk1 and Cds1 respond to different checkpoint signals.
Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
Six checkpoint Rad proteins (Rad1, Rad3, Rad9, Rad17, Rad26, and Hus1) are needed to regulate checkpoint protein kinases Chk1 and Cds1 in fission yeast. Chk1 is required to prevent mitosis when DNA is damaged by ionizing radiation (IR), whereas either kinase is sufficient to prevent mitosis when DNA replication is inhibited by hydroxyurea (HU). Checkpoint Rad proteins are required for IR-induced phosphorylation of Chk1 and HU-induced activation of Cds1. IR activates Cds1 only during the DNA synthesis (S) phase, whereas HU induces Chk1 phosphorylation only in cds1 mutants. Here, we investigate the basis of the checkpoint signal specificity of Chk1 phosphorylation and Cds1 activation. We show that IR fails to induce Chk1 phosphorylation in HU-arrested cells. Release from the HU arrest following IR causes substantial Chk1 phosphorylation. These and other data indicate that Cds1 prevents Chk1 phosphorylation in HU-arrested cells, which suggests that Cds1 actively suppresses a repair process that leads to Chk1 phosphorylation. Cds1 becomes more highly concentrated in the nucleus only during the S phase of the cell cycle. This finding correlates with S-phase specificity of IR-induced activation of Cds1. However, constitutive nuclear localization of Cds1 does not enhance IR-induced activation of Cds1. This result suggests that Cds1 activation requires DNA structures or protein activities that are present only during S phase. These findings help to explain how Chk1 and Cds1 respond to different checkpoint signals.
Author Michael N. Boddy
Beth Furnari
Paul Russell
Jean-Marc Brondello
AuthorAffiliation Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037
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Corresponding author. Mailing address: Department of Molecular Biology MB3, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8273. Fax: (619) 784-2265. E-mail: prussell@scripps.edu.
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Six checkpoint Rad proteins (Rad1, Rad3, Rad9, Rad17, Rad26, and Hus1) are needed to regulate checkpoint protein kinases Chk1 and Cds1 in fission yeast. Chk1...
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StartPage 4262
SubjectTerms Cell Cycle - physiology
Cell Growth and Development
Cell Nucleus - metabolism
Checkpoint Kinase 1
Checkpoint Kinase 2
DNA Repair - physiology
Enzyme Inhibitors - pharmacology
GTP-Binding Proteins - physiology
Hydroxyurea - pharmacology
Immunoblotting
Phosphorylation
Protein Kinases - physiology
Protein-Serine-Threonine Kinases
ras Proteins
Recombinant Fusion Proteins
S Phase - physiology
Schizosaccharomyces - physiology
Schizosaccharomyces pombe
Schizosaccharomyces pombe Proteins
Time Factors
Title Basis for the Checkpoint Signal Specificity That Regulates Chk1 and Cds1 Protein Kinases
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https://www.tandfonline.com/doi/abs/10.1128/MCB.19.6.4262
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https://search.proquest.com/docview/17222838
https://search.proquest.com/docview/69762905
https://pubmed.ncbi.nlm.nih.gov/PMC104386
Volume 19
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