title: Regulation of alternative replication bypass pathways at stalled replication forks and its effects on genome stability: a yeast model.
abstract: Replication-blocking lesions result in increased genomic instability by stalling replication forks. Eukaryotic cells appear to have evolved several surveillance and repair/bypass mechanisms to ensure that replication can be resumed at these stalled forks. In the yeast Saccharomyces cerevisiae, the helicases Srs2 and Sgs1 appear to play a role in controlling the processing and stabilization of stalled replication forks. These proteins appear to be tightly regulated throughout the cell cycle and play a direct role in DNA-damage checkpoints. This allows the cells to determine the best mechanism to reestablish replication at the stalled fork: by shuttling the lesion into the RAD6-dependent pathway that can lead to error-free or error-prone bypass; or by using homologous recombination. Under conditions where both the RAD6-dependent pathway and recombination are disabled, the cells can bypass the lesion using a novel damage avoidance mechanism that is controlled by Mgs1. Replication fork bypass processes appear to be highly conserved within eukaryotes, with homologs for SGS1 and MGS1 found in both Schizosaccharomyces pombe and mammalian cells.
authors.affiliation: Department of Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.
authors.forename: Leslie
authors.initials: L
authors.lastname: Barbour
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D003434:Crossing Over, Genetic; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication; D004271:DNA, Fungal / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D042822:Genomic Instability; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D015398:Signal Transduction
chemical_list: D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D004265:DNA Helicases