An Intrinsic Cell Cycle Checkpoint Pathway Mediated by MEK and ERK in Drosophila

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 demo...

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Bibliographic Details
Published in:Developmental cell 2006-10, Vol.11 (4), p.575-582
Main Authors: Mogila, Vladic, Xia, Fan, Li, Willis X.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Cycle - physiology
Cell cycle, cell proliferation
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
CELLCYCLE
DEVBIO
Drosophila
Drosophila - embryology
Drosophila - genetics
Drosophila - metabolism
Drosophila - radiation effects
Embryo, Nonmammalian
Enzyme Activation
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic
Immunohistochemistry
Kinetics
Mitogen-Activated Protein Kinase Kinases - genetics
Mitogen-Activated Protein Kinase Kinases - metabolism
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Models, Biological
Molecular and cellular biology
Radiation, Ionizing
RNA, Messenger - biosynthesis
SIGNALING
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Summary: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.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2006.08.010