Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1- and Rad53-dependent checkpoint in budding yeast
| Autor: | Holger Neecke, Giovanna Lucchini, Maria Pia Longhese |
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| Rok vydání: | 1999 |
| Předmět: |
DNA Replication
DNA re-replication Saccharomyces cerevisiae Proteins Cell cycle checkpoint Ultraviolet Rays DNA repair Cell Cycle Proteins Eukaryotic DNA replication Saccharomyces cerevisiae Protein Serine-Threonine Kinases Biology Pre-replication complex General Biochemistry Genetics and Molecular Biology S Phase Fungal Proteins Control of chromosome duplication CHEK1 Phosphorylation DNA Fungal Molecular Biology General Immunology and Microbiology General Neuroscience Cell Cycle G1 Phase Intracellular Signaling Peptides and Proteins G2-M DNA damage checkpoint Molecular biology Cell biology Checkpoint Kinase 2 DNA Repair Enzymes Protein Kinases Gene Deletion DNA Damage Signal Transduction Research Article |
| Zdroj: | The EMBO Journal. 18:4485-4497 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/18.16.4485 |
| Popis: | We studied the response of nucleotide excision repair (NER)-defective rad14Delta cells to UV irradiation in G(1) followed by release into the cell cycle. Only a subset of checkpoint proteins appears to mediate cell cycle arrest and regulate the timely activation of replication origins in the presence of unrepaired UV-induced lesions. In fact, Mec1 and Rad53, but not Rad9 and the Rad24 group of checkpoint proteins, are required to delay cell cycle progression in rad14Delta cells after UV damage in G(1). Consistently, Mec1-dependent Rad53 phosphorylation after UV irradiation takes place in rad14Delta cells also in the absence of Rad9, Rad17, Rad24, Mec3 and Ddc1, and correlates with entry into S phase. Two-dimensional gel analysis indicates that late replication origins are not fired in rad14Delta cells UV-irradiated in G(1) and released into the cell cycle, which instead initiate DNA replication from early origins and accumulate replication and recombination intermediates. Progression through S phase of UV-treated NER-deficient mec1 and rad53 mutants correlates with late origin firing, suggesting that unregulated DNA replication in the presence of irreparable UV-induced lesions might result from a failure to prevent initiation at late origins. |
| Databáze: | OpenAIRE |
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