The novel DNA damage checkpoint protein ddc1p is phosphorylated periodically during the cell cycle and in response to DNA damage in budding yeast.
The DDC1 gene was identified, together with MEC3 and other checkpoint genes, during a screening for mutations causing synthetic lethality when combined with a conditional allele altering DNA primase. Deletion of DDC1 causes sensitivity to UV radiation, methyl methanesulfonate (MMS) and hydroxyurea (HU). ddc1Delta mutants are defective in delaying G1-S and G2-M transition and in slowing down the rate of DNA synthesis when DNA is damaged during G1, G2 or S phase, respectively. Therefore, DDC1 is involved in all the known DNA damage checkpoints. Conversely, Ddc1p is not required for delaying entry into mitosis when DNA synthesis is inhibited. ddc1 and mec3 mutants belong to the same epistasis group, and DDC1 overexpression can partially suppress MMS and HU sensitivity of mec3Delta strains, as well as their checkpoint defects. Moreover, Ddc1p is phosphorylated periodically during a normal cell cycle and becomes hyperphosphorylated in response to DNA damage. Both phosphorylation events are at least partially dependent on a functional MEC3 gene.
Longhese
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MP
Dipartimento di Genetica e di Biologia dei Microrganismi, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Paciotti
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V
Fraschini
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Zaccarini
R
R
Plevani
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P
Lucchini
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G
D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004249:DNA Damage; D004843:Epistasis, Genetic; D005800:Genes, Fungal; D006023:Glycoproteins / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D008741:Methyl Methanesulfonate; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology; D010507:Periodicity; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D014466:Ultraviolet Rays / Q000009:adverse effects
D018797:Cell Cycle Proteins; D006023:Glycoproteins; C099938:MEC3 protein, S cerevisiae; D009153:Mutagens; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D006918:Hydroxyurea