Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time.
The major mission of the cell division cycle is a faithful and complete duplication of the genome followed by an equal partitioning of chromosomes to subsequent cell generations. In this review, we discuss the advances in our understanding of how mammalian cells control the fidelity of these fundamental processes when exposed to diverse genotoxic insults. We focus on the most recent insights into the molecular pathways that link the sites of DNA lesions with the cell cycle machinery in specific phases of the cell cycle. We also highlight the potential of a new technology allowing direct visualization of molecular interactions and redistribution of checkpoint proteins in live cell nuclei, and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal organization of the DNA damage response network.
Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
Jiri
J
Lukas
Claudia
C
Lukas
Jiri
J
Bartek
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D016193:G1 Phase; D016195:G2 Phase; D016678:Genome; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction; D013997:Time Factors
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D004247:DNA; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases