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PMID: 9311982 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The novel DNA damage checkpoint protein ddc1p is phosphorylated periodically during the cell cycle and in response to DNA damage in budding yeast.

The EMBO journal ·Vol. 16 ·No. 17 ·1997-09-01 ·Pages 5216-26

Longhese MP, Paciotti V, Fraschini R, Zaccarini R, Plevani P, Lucchini G

Abstract

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.

MeSH Terms
Cell Cycle/genetics Cell Cycle Proteins/genetics,metabolism Cloning, Molecular DNA Damage Epistasis, Genetic Genes, Fungal Glycoproteins/pharmacology Hydroxyurea/pharmacology Methyl Methanesulfonate Mutagenesis Mutagens/pharmacology Periodicity Phosphoproteins/metabolism Phosphorylation Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Suppression, Genetic Ultraviolet Rays/adverse effects
Chemicals
Cell Cycle Proteins Glycoproteins MEC3 protein, S cerevisiae Mutagens Phosphoproteins Saccharomyces cerevisiae Proteins Methyl Methanesulfonate Hydroxyurea
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Longhese M P
Dipartimento di Genetica e di Biologia dei Microrganismi, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Paciotti V
Fraschini R
Zaccarini R
Plevani P
Lucchini G
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.17.5216
Published
1997-09-01
Pages
5216-26
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170154
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/16.17.5216 PMC Full Text View journal details
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