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PMID: 9001228 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2.

Molecular and cellular biology ·Vol. 17 ·No. 2 ·1997-02-00 ·Pages 742-50

Matsumoto T

Abstract

Successful recovery from DNA damage requires coordination of several biological processes. Eukaryotic cell cycle progression is delayed when the cells encounter DNA-damaging agents. This cell cycle delay allows the cells to cope with DNA damage by utilizing DNA repair enzymes. Thus, at least two processes, induction of the cell cycle delay and repair of damaged DNA, are coordinately required for recovery. In this study, a fission yeast rad mutant (slp1-362) was genetically investigated. In response to radiation, slp1 stops cell division; however, it does not restart it. This defect is suppressed when slp1-362 is combined with wee1-50 or cdc2-3w; in these mutants, the onset of mitosis is advanced due to the premature activation of p34cdc2. In contrast, slp1 is synthetically lethal with cdc25, nim1/cdr1, or cdr2, all of which are unable to activate the p34cdc2 kinase correctly. These genetic interactions of slp1 with cdc2 and its modulators imply that slp1 is not defective in either "induction of cell cycle delay" or "DNA repair." slp1+ may be involved in a critical process which restarts cell cycle progression after the completion of DNA repair. Molecular cloning of slp1+ revealed that slp1+ encodes a putative 488-amino-acid polypeptide exhibiting significant homology to WD-domain proteins, namely, CDC20 (budding yeast), p55CDC (human), and Fizzy (fly). A possible role of slp1+ is proposed.

MeSH Terms
Amino Acid Sequence CDC2 Protein Kinase/genetics Carrier Proteins/genetics,physiology Cdc20 Proteins Cell Cycle/genetics Cell Cycle Proteins/genetics Cell Division Cloning, Molecular DNA Damage/physiology Endonucleases/genetics Fungal Proteins/genetics,physiology Genes, Lethal Mitosis Molecular Sequence Data Mutation Nuclear Proteins Phenotype Protein-Tyrosine Kinases/genetics Saccharomyces cerevisiae Proteins Schizosaccharomyces/genetics,physiology,radiation effects Schizosaccharomyces pombe Proteins Sequence Homology, Amino Acid Single-Strand Specific DNA and RNA Endonucleases Spores, Fungal Suppression, Genetic Temperature Ultraviolet Rays
Chemicals
Carrier Proteins Cdc20 Proteins Cell Cycle Proteins Fungal Proteins Nuclear Proteins Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins slp1 protein, S pombe CDC20 protein, human wee1 protein, S pombe Protein-Tyrosine Kinases CDC2 Protein Kinase Endonucleases RAD10 protein, S cerevisiae Single-Strand Specific DNA and RNA Endonucleases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Matsumoto T
Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. tmatsumo@aecom.yu.edu
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.2.742
Email
tmatsumo@aecom.yu.edu
Published
1997-02-00
Pages
742-50
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231800
Subset
IM
Databases
GENBANK
U77983
External Links
PubMed source DOI: 10.1128/MCB.17.2.742 PMC Full Text View journal details
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