rad-Dependent Response of the chk1-Encoded Protein Kinase at the DNA Damage Checkpoint

Exposure of eukaryotic cells to agents that generate DNA damage results in transient arrest of progression through the cell cycle. In fission yeast, the DNA damage checkpoint associated with cell cycle arrest before mitosis requires the protein kinase p56$^{chk1}$. DNA damage induced by ultraviolet...

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Published in:Science (American Association for the Advancement of Science) 1996-01, Vol.271 (5247), p.353-356
Main Authors: Walworth, Nancy C., Bernards, Rene
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - genetics
Alleles
Ataxia Telangiectasia Mutated Proteins
Base Sequence
Biological and medical sciences
Cell cycle
Cell Cycle Proteins
Cellular biology
Checkpoint Kinase 1
Complementary DNA
Deoxyribonucleic acid
DNA
DNA Damage
DNA Helicases - genetics
DNA Replication
DNA, Fungal - metabolism
DNA, Fungal - radiation effects
DNA-Binding Proteins
Electrophoresis, Polyacrylamide Gel
Epitopes
Fundamental and applied biological sciences. Psychology
G2 Phase
Gamma rays
Genes, Fungal
Humans
Light
Mitosis
Mobility
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Mutagenesis. Repair
Mutation
Observation
Phosphorylation
Physiological aspects
Protein Kinases - chemistry
Protein Kinases - genetics
Protein Kinases - metabolism
Protein-Serine-Threonine Kinases
Proteins
Proteins - genetics
Radiation
Radiation damage
Radiation dosage
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - metabolism
Saccharomyces cerevisiae Proteins
Schizosaccharomyces - cytology
Schizosaccharomyces - genetics
Schizosaccharomyces - radiation effects
Schizosaccharomyces pombe
Schizosaccharomyces pombe Proteins
Tumor Suppressor Proteins
Ultraviolet Rays
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Bernards, Rene
description Exposure of eukaryotic cells to agents that generate DNA damage results in transient arrest of progression through the cell cycle. In fission yeast, the DNA damage checkpoint associated with cell cycle arrest before mitosis requires the protein kinase p56$^{chk1}$. DNA damage induced by ultraviolet light, gamma radiation, or a DNA-alkylating agent has now been shown to result in phosphorylation of p56$^{chk1}$. This phosphorylation decreased the mobility of p56$^{chk1}$ on SDS-polyacrylamide gel electrophoresis and was abolished by a mutation in the p56$^{chk1}$ catalytic domain, suggesting that it might represent autophosphorylation. Phosphorylation of p56$^{chk1}$ did not occur when other checkpoint genes were inactive. Thus, p56$^{chk1}$ appears to function downstream of several of the known Schizosaccharomyces pombe checkpoint gene products, including that encoded by rad3$^+$, a gene with sequence similarity to the ATM gene mutated in patients with ataxia telangiectasia. The phosphorylation of p56$^{chk1}$ provides an assayable biochemical response to activation of the DNA damage checkpoint in the G$_2$ phase of the cell cycle.
doi_str_mv 10.1126/science.271.5247.353
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In fission yeast, the DNA damage checkpoint associated with cell cycle arrest before mitosis requires the protein kinase p56$^{chk1}$. DNA damage induced by ultraviolet light, gamma radiation, or a DNA-alkylating agent has now been shown to result in phosphorylation of p56$^{chk1}$. This phosphorylation decreased the mobility of p56$^{chk1}$ on SDS-polyacrylamide gel electrophoresis and was abolished by a mutation in the p56$^{chk1}$ catalytic domain, suggesting that it might represent autophosphorylation. Phosphorylation of p56$^{chk1}$ did not occur when other checkpoint genes were inactive. Thus, p56$^{chk1}$ appears to function downstream of several of the known Schizosaccharomyces pombe checkpoint gene products, including that encoded by rad3$^+$, a gene with sequence similarity to the ATM gene mutated in patients with ataxia telangiectasia. 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In fission yeast, the DNA damage checkpoint associated with cell cycle arrest before mitosis requires the protein kinase p56$^{chk1}$. DNA damage induced by ultraviolet light, gamma radiation, or a DNA-alkylating agent has now been shown to result in phosphorylation of p56$^{chk1}$. This phosphorylation decreased the mobility of p56$^{chk1}$ on SDS-polyacrylamide gel electrophoresis and was abolished by a mutation in the p56$^{chk1}$ catalytic domain, suggesting that it might represent autophosphorylation. Phosphorylation of p56$^{chk1}$ did not occur when other checkpoint genes were inactive. Thus, p56$^{chk1}$ appears to function downstream of several of the known Schizosaccharomyces pombe checkpoint gene products, including that encoded by rad3$^+$, a gene with sequence similarity to the ATM gene mutated in patients with ataxia telangiectasia. The phosphorylation of p56$^{chk1}$ provides an assayable biochemical response to activation of the DNA damage checkpoint in the G$_2$ phase of the cell cycle.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>8553071</pmid><doi>10.1126/science.271.5247.353</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record>
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1095-9203
language eng
recordid cdi_proquest_miscellaneous_36196568
source American Association for the Advancement of Science; Education Collection (Proquest) (PQ_SDU_P3); Social Science Premium Collection (Proquest) (PQ_SDU_P3); JSTOR
subjects Adenosine Triphosphatases - genetics
Alleles
Ataxia Telangiectasia Mutated Proteins
Base Sequence
Biological and medical sciences
Cell cycle
Cell Cycle Proteins
Cellular biology
Checkpoint Kinase 1
Complementary DNA
Deoxyribonucleic acid
DNA
DNA Damage
DNA Helicases - genetics
DNA Replication
DNA, Fungal - metabolism
DNA, Fungal - radiation effects
DNA-Binding Proteins
Electrophoresis, Polyacrylamide Gel
Epitopes
Fundamental and applied biological sciences. Psychology
G2 Phase
Gamma rays
Genes, Fungal
Humans
Light
Mitosis
Mobility
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Mutagenesis. Repair
Mutation
Observation
Phosphorylation
Physiological aspects
Protein Kinases - chemistry
Protein Kinases - genetics
Protein Kinases - metabolism
Protein-Serine-Threonine Kinases
Proteins
Proteins - genetics
Radiation
Radiation damage
Radiation dosage
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - metabolism
Saccharomyces cerevisiae Proteins
Schizosaccharomyces - cytology
Schizosaccharomyces - genetics
Schizosaccharomyces - radiation effects
Schizosaccharomyces pombe
Schizosaccharomyces pombe Proteins
Tumor Suppressor Proteins
Ultraviolet Rays
title rad-Dependent Response of the chk1-Encoded Protein Kinase at the DNA Damage Checkpoint
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T18%3A23%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=rad-Dependent%20Response%20of%20the%20chk1-Encoded%20Protein%20Kinase%20at%20the%20DNA%20Damage%20Checkpoint&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Walworth,%20Nancy%20C.&rft.date=1996-01-19&rft.volume=271&rft.issue=5247&rft.spage=353&rft.epage=356&rft.pages=353-356&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.271.5247.353&rft_dat=%3Cgale_proqu%3EA17979823%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c792t-9bafd66b22b056b9ae9e2163b8e4e55b66a6ca19ba9628f326d8aaa9cf1d0e743%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=213555457&rft_id=info:pmid/8553071&rft_galeid=A17979823&rft_jstor_id=2890469&rfr_iscdi=true