Replication origins: why do we need so many?
During the G1 phase of the cell cycle, replication origins are prepared to fire, a process that is referred to as origin licensing. It was often pondered what a cell's fate would be if not all of its replication origins were licensed and subsequently activated during S phase. One obvious prediction was that S phase would simply be prolonged. As it turns out, however, the consequences are much more complex. A short G1 phase enforced by premature entry into S phase, or other events that negatively affect origin licensing, will ultimately compromise the cell's ability to complete DNA replication before entering mitosis. As a result, the cell becomes genomically unstable when it attempts to repair unreplicated DNA during anaphase. Thus, the density of active replication origins in the chromosomes of eukaryotic cells determines S phase dynamics and chromosome stability during mitosis.
Bielinsky
Anja-Katrin
AK
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Molecular and Cellular Biology Building, Room 6-106, 420 Washington Ave SE, Minneapolis, Minnesota 55455, USA. bielinsk@cbs.umn.edu
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008938:Mitosis / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism; D051738:Origin Recognition Complex; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018741:Replication Origin / Q000502:physiology*; D016196:S Phase / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051738:Origin Recognition Complex; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases