Exp Mol Med.  2005 Jun;37(3):255-260.

Sec13 induces genomic instability in U2OS cells

• Sihn CR
• Suh EJ
• Lee KH
• Kim SH

Abstract

Sec13p has been known as an endoplasmic reticulum-Golgi transport protein. Recently, it has also been shown to be required for the formation of septation in the fission yeast Schizosaccharomyces pombe. In the present study, we focused on the role of a human homolog of Saccharomyces cerevisiae SEC13, Sec13 protein during mitosis in U2OS cells. We found that the expression of Sec13 was constant throughout the cell cycle, and localized to the kinetochores at metaphase during mitosis. By using green fluorescent protein technology, we observed that Sec13 is required for evasion of mitotic arrest in response to spindle damage, leading to G1-like phase and apoptotic cell death. In addition, cells expressing exogenous Sec13 showed giant nuclei compared to endogenous ones in the absence of nocodazole. These results demonstrate that Sec13 is involved in the regulation of the metaphase/anaphase transition and may be functionally associated with mitotic machinery to maintain genomic stability during mitosis.

Keyword

Sec13; mitosis; genomic instability; U2OS cells; nuclear pore complex

MeSH Terms

Anaphase
Antineoplastic Agents/pharmacology
Cell Line, Tumor/drug effects/metabolism/pathology
*G1 Phase
*Genomic Instability
Green Fluorescent Proteins/metabolism
Humans
Kinetochores/metabolism
Membrane Proteins/*genetics/metabolism
Metaphase
Mitosis/*physiology
*Mitotic Spindle Apparatus
Nocodazole/pharmacology
Osteosarcoma/genetics/metabolism/pathology
Research Support, Non-U.S. Gov't