Chk1-controlled and DNA-damage induced centrosome duplication

Stable Identifier
R-GGA-217106
Type
Pathway
Species
Gallus gallus
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Chk1-controlled and DNA-damage induced centrosome duplication
Click the image above or here to open this pathway in the Pathway Browser
Centrosomal abnormalities are frequently observed in cancers and in cells with defective DNA repair. Chk1 controlled centrosome duplication is a general response to DNA damage in tumor cells, especially in cells arrested at the G2-M phase of the cell cycle or in an extended S-phase under conditions of hydroxyurea-induced replication stress. Chicken DT40 cells expressing kinase-dead (D130A) or phosphorylation site(S345A) Chk1 mutants, or cells in which Chk1 levels were knocked down, did not show centrosome overduplication, indicating an essential role of Chk1 catalytic activity in this process. The centrosomal localization of human Chk1 also indicates a potential role at the centrosome. It is still unclear whether the actual role for Chk1 signaling is to cause a cell-cycle delay, or if Chk1 directly affects centromere amplification upon DNA damage. A role for Cdc25-mediated regulation of Cdk2 (cyclin dependent kinase2) acting downstream of Chk1 has also been implicated.
Literature References
PubMed ID Title Journal Year
17468739 DNA damage induces Chk1-dependent centrosome amplification

Walker, M, Cuffe, L, Dodson, H, Gillespie, D, Merdes, A, Zachos, G, Morrison, CG, Bourke, E

EMBO Rep 2007
15311285 Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase

Sylju?sen, RG, Lukas, J, Nigg, EA, Kramer, A, Lukas, C, Bartek, J, Wilkinson, CJ, Mailand, N

Nat Cell Biol 2004
Participants
Events
Participates
as an event of
Authored
Saxena, A  (2008-01-04)
Reviewed
Borowiec, JA  (2009-04-24)
Created
Saxena, A  (2008-03-26)
Cite Us!