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Centrosomal Che-1 protein is involved in the regulation of mitosis and DNA damage response by mediating pericentrin (PCNT)-dependent Chk1 protein localization.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2013 Aug 09; Vol. 288 (32), pp. 23348-57. Date of Electronic Publication: 2013 Jun 24. - Publication Year :
- 2013
-
Abstract
- To combat threats posed by DNA damage, cells have evolved mechanisms, collectively termed DNA damage response (DDR). These mechanisms detect DNA lesions, signal their presence, and promote their repair. Centrosomes integrate G2/M checkpoint control and repair signals in response to genotoxic stress, acting as an efficient control mechanism when G2/M checkpoint function fails and mitosis begins in the presence of damaged DNA. Che-1 is an RNA polymerase II-binding protein involved in the regulation of gene transcription, induction of cell proliferation, and DDR. Here we provide evidence that in addition to its nuclear localization, Che-1 localizes at interphase centrosomes, where it accumulates following DNA damage or spindle poisons. We show that Che-1 depletion generates supernumerary centrosomes, multinucleated cells, and multipolar spindle formation. Notably, Che-1 depletion abolishes the ability of Chk1 to bind pericentrin and to localize at centrosomes, which, in its turn, deregulates the activation of centrosomal cyclin B-Cdk1 and advances entry into mitosis. Our results reinforce the notion that Che-1 plays an important role in DDR and that its contribution seems to be relevant for the spindle assembly checkpoint.
- Subjects :
- Antigens genetics
Apoptosis Regulatory Proteins genetics
CDC2 Protein Kinase genetics
CDC2 Protein Kinase metabolism
Cell Line, Tumor
Checkpoint Kinase 1
Chromosomes, Human genetics
Cyclin B genetics
Cyclin B metabolism
G2 Phase Cell Cycle Checkpoints physiology
Humans
M Phase Cell Cycle Checkpoints physiology
Protein Kinases genetics
Repressor Proteins genetics
Antigens metabolism
Apoptosis Regulatory Proteins metabolism
Centrosome metabolism
Chromosomes, Human metabolism
DNA Damage
Mitosis physiology
Protein Kinases metabolism
Repressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 288
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23798705
- Full Text :
- https://doi.org/10.1074/jbc.M113.465302