title: An intrinsic cell cycle checkpoint pathway mediated by MEK and ERK in Drosophila.
abstract: Cell cycle checkpoints are surveillance mechanisms that safeguard genome integrity. While the extrinsic pathways that halt the cell cycle in response to DNA damages have been well documented, the intrinsic pathways that ensure orderly progression of cell cycle events are not well understood. We demonstrate that Drosophila MEK and ERK constitute an essential intrinsic checkpoint pathway that restrains cell cycle progression in the absence of DNA damage and also responds to ionizing radiation to arrest the cell cycle. Embryos lacking MEK exhibit faster and extra division cycles and fail to undergo timely midblastula transition (MBT) or arrest following ionizing radiation. Conversely, constitutively activated MEK causes cell cycle arrest. Further, MEK activation in the early embryo is cell cycle-dependent and Raf independent and increases in response to ionizing radiation or in the absence of Chk1. Thus, MEK/ERK activation is required for multiple checkpoints and is essential for orderly cell cycle progression.
authors.affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Vladic
authors.initials: V
authors.lastname: Mogila
authors.forename: Fan
authors.initials: F
authors.lastname: Xia
authors.forename: Willis X
authors.initials: WX
authors.lastname: Li
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D004625:Embryo, Nonmammalian; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D007700:Kinetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D012333:RNA, Messenger / Q000096:biosynthesis; D011839:Radiation, Ionizing
chemical_list: D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases