PMID:22363533

Citation	Thanasopoulou, A, Stravopodis, DJ, Dimas, KS, Schwaller, J and Anastasiadou, E (2012) Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control. PLoS ONE 7:e31007
Abstract	In most cancers harboring Ccdc6 gene rearrangements, like papillary thyroid tumors or myeloproliferative disorders, the product of the normal allele is supposed to be functionally impaired or absent. To address the consequence of the loss of CCDC6 expression, we applied lentiviral shRNA in several cell lines. Loss of CCDC6 resulted in increased cell death with clear shortening of the S phase transition of the cell cycle. Upon exposure to etoposide, the cells lacking CCDC6 did not achieve S-phase accumulation. In the absence of CCDC6 and in the presence of genotoxic stress, like etoposide treatment or UV irradiation, increased accumulation of DNA damage was observed, as indicated by a significant increase of pH2Ax Ser139. 14-3-3σ, a major cell cycle regulator, was down-regulated in CCDC6 lacking cells, regardless of genotoxic stress. Interestingly, in the absence of CCDC6, the well-known genotoxic stress-induced cytoplasmic sequestration of the S-phase checkpoint CDC25C phosphatase did not occur. These observations suggest that CCDC6 plays a key role in cell cycle control, maintenance of genomic stability and cell survival and provide a rational of how disruption of CCDC6 normal function contributes to malignancy.
Links	PubMed PMC3281900 Online version:10.1371/journal.pone.0031007
Keywords	14-3-3 Proteins/metabolism; Cell Death/drug effects; Cell Death/radiation effects; Cell Line, Tumor; Cell Proliferation/drug effects; Cell Proliferation/radiation effects; Cytoskeletal Proteins/deficiency; Cytoskeletal Proteins/metabolism; DNA Damage; Etoposide/pharmacology; Exonucleases/metabolism; G2 Phase/drug effects; G2 Phase/radiation effects; Gene Knockdown Techniques; Gene Silencing/drug effects; Gene Silencing/radiation effects; Humans; Mitosis/drug effects; Mitosis/radiation effects; Protein Transport/drug effects; Protein Transport/radiation effects; S Phase Cell Cycle Checkpoints/drug effects; S Phase Cell Cycle Checkpoints/radiation effects; Tumor Markers, Biological/metabolism; Ultraviolet Rays; cdc25 Phosphatases/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:Q05CP8		GO:0007090: regulation of S phase of mitotic cell cycle	ECO:0000315:		P		see Figure 2 in paper to see the experiment done to show that the protein is used to regulate the S phase of mitotic cell cycle	complete CACAO 7388

References

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