title: An intrinsic checkpoint model for regulation of replication origins.
abstract: A recent paper by Alvino et al., (MCB 2007; 27:6396) challenges the standard model of the DNA replication checkpoint. Their work shows that the checkpoint does not simply prevent late origins from firing in the presence of the nucleotide synthesis inhibitor hydroxyurea; instead it delays origin firing to maintain the regular order of origin firing relative to the now much slower rate of fork elongation. To explain these results, this perspective proposes a model in which the timing of origin firing is intrinsically coupled to the rate of fork elongation by the fact that late origins can only fire after early forks have terminated and released some essential replisome factor. This coupling fails in a checkpoint mutant background because stalled forks disassemble and release replisome factors prematurely, allowing for unregulated origin firing.
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. nick.rhind@umassmed.edu
authors: Nicholas
authors: N
authors: Rhind
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018741:Replication Origin / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D006918:Hydroxyurea