DNA structure-dependent checkpoints in model systems.
DNA structure dependent checkpoints require a number of proteins which function to arrest the cell cycle in response to DNA damage (such as UV induced lesions) or blocks to DNA replication. Analogous to a signal transduction pathway, checkpoints communicate information between a DNA lesion and the cell cycle machinery. This brief review will focus on yeast model systems which have been instrumental in identifying the various components (initiating signal, detection, signal transduction and cell cycle effector) of the checkpoint pathways. The biological significance of these pathways in mammalian cells is illustrated in patients with ataxia telangiectasia (AT), a multi-system cancer-prone disorder in which DNA damage checkpoints affecting both DNA replication and mitosis are lost. ATM, the gene mutated in this disorder is structurally related to the yeast rad3/MEC1 checkpoint genes. This demonstrates the high degree of evolutionary conservation of checkpoints amongst eukaryotic organisms.
Bentley
N J
NJ
MRC Cell Mutation Unit, Sussex University, Falmer, UK.
Carr
A M
AM
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins; D006801:Humans; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases; C061897:Rad3 protein, S cerevisiae; D004265:DNA Helicases