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PMID:18843199
| Citation |
Chen, Y, Chen, PL, Chen, CF, Jiang, X and Riley, DJ (2008) Never-in-mitosis related kinase 1 functions in DNA damage response and checkpoint control. Cell Cycle 7:3194-201 |
|---|---|
| Abstract |
Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1(-/-) mice fail to arrest properly at G(1)/S and M-phase checkpoints in response to DNA damage. G(1)-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1(-/-) murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair. |
| Links | |
| Keywords |
Animals; Cell Cycle/physiology; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cell Line; DNA/drug effects; DNA/radiation effects; DNA Damage; DNA Repair; Enzyme Activation; Humans; Mice; Mice, Knockout; Protein Kinases/genetics; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; RNA Interference; Radiation, Ionizing; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Ultraviolet Rays |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:2000001: regulation of DNA damage checkpoint |
ECO:0000315: |
P |
Figure 2a shows specific Nek1 expression in Nek1−/− mutants restores ability to arrest cell cell development when dna damage is present. |
complete | ||||
|
involved_in |
GO:2000001: regulation of DNA damage checkpoint |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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