Increased genome instability and telomere length in the elg1-deficient Saccharomyces cerevisiae mutant are regulated by S-phase checkpoints.

Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A22, Bethesda, MD 20892, USA.
Gross chromosomal rearrangements (GCRs) are frequently observed in cancer cells. Abnormalities in different DNA metabolism including DNA replication, cell cycle checkpoints, chromatin remodeling, telomere maintenance, and DNA recombination and repair cause GCRs in Saccharomyces cerevisiae. Recently, we used genome-wide screening to identify several genes the deletion of which increases GCRs in S. cerevisiae. Elg1, which was discovered during this screening, functions in DNA replication by participating in an alternative replication factor complex. Here we further characterize the GCR suppression mechanisms observed in the elg1Delta mutant strain in conjunction with the telomere maintenance role of Elg1. The elg1Delta mutation enhanced spontaneous DNA damage and resulted in GCR formation. However, DNA damage due to inactivation of Elg1 activates the intra-S checkpoints, which suppress further GCR formation. The intra-S checkpoints activated by the elg1Delta mutation also suppress GCR formation in strains defective in the DNA replication checkpoint. Lastly, the elg1Delta mutation increases telomere size independently of other previously known telomere maintenance proteins such as the telomerase inhibitor Pif1 or the telomere size regulator Rif1. The increase in telomere length caused by the elg1Delta mutation was suppressed by a defect in the DNA replication checkpoint, which suggests that DNA replication surveillance by Dpb11-Mec1/Tel1-Dun1 also has an important role in telomere length regulation.
Mesh Terms:
Base Sequence, Carrier Proteins, DNA, DNA Damage, DNA Helicases, DNA Repair, DNA Replication, DNA-Binding Proteins, Gene Deletion, Genome, Fungal, Genomic Instability, Methyl Methanesulfonate, Molecular Sequence Data, Mutagens, Mutation, Recombination, Genetic, Repressor Proteins, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Nucleic Acid, Telomere, Telomere-Binding Proteins, Time Factors
Eukaryotic Cell Dec. 01, 2004; 3(6);1557-66 [PUBMED:15590829]
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