RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway in budding yeast normally required for Rad53 modification and activation. 1998

M A de la Torre-Ruiz, and C M Green, and N F Lowndes
Imperial Cancer Research Fund, Clare Hall Laboratories, CDC Laboratory, South Mimms, Herts EN6 3LD, UK.

In budding yeast, RAD9 and RAD24/RAD17/MEC3 are believed to function upstream of MEC1 and RAD53 in signalling the presence of DNA damage. Deletion of any one of these genes reduces the normal G1/S and G2/M checkpoint delays after UV irradiation, whereas in rad9Delta-rad24Delta cells the G1/S checkpoint is undetectable, although there is a residual G2/M checkpoint. We have shown previously that RAD9 also controls the transcriptional induction of a DNA damage regulon (DDR). We now report that efficient DDR induction requires all the above-mentioned checkpoint genes. Residual induction of the DDR after UV irradiation observed in all single mutants is not detectable in rad9Delta-rad24Delta. We have examined the G2/M checkpoint and UV sensitivity of single mutants after overexpression of the checkpoint proteins. This analysis indicates that RAD9 and the RAD24 epistasis group can be placed onto two separate, additive branches that converge on MEC1 and RAD53. Furthermore, MEC3 appears to function downstream of RAD24/RAD17. The transcriptional response to DNA damage revealed unexpected and specific antagonism between RAD9 and RAD24. Further support for genetic interaction between RAD9 and RAD24 comes from study of the modification and activation of Rad53 after damage. Evidence for bypass of RAD53 function under some conditions is also presented.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008938 Mitosis A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004271 DNA, Fungal Deoxyribonucleic acid that makes up the genetic material of fungi. Fungal DNA
D005090 Exodeoxyribonucleases A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products. DNA Exonucleases,Exonucleases, DNA

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