TLK-1 functions in DNA condensation, segregation and cytokinesis in Caenorhaditis elegans
Date Issued
2010
Date
2010
Author(s)
Yeh, Chan-Hsien
Abstract
Defects in chromosome condensation, segregation or cytokinesis during mitosis disrupt genome integrity and cause organismal death or tumorigenesis. The conserved kinase protein AIR-2/Aurora B is required for normal execution of all these important mitotic events in C. elegans. TLK-1 has been recently shown to be a substrate and activator of AIR-2 in the presence of another AIR-2 activator ICP-1/INCENP, and to cooperate with AIR-2 to ensure proper mitotic chromosome segregation. However, whether TLK-1 may contribute to chromosome condensation or cytokinesis is unclear. A time-lapse microscopy analysis showed that tlk-1 mutants are defective in chromosome condensation and cytokinesis, in addition to chromosome segregation, during mitosis. Our data indicate that TLK-1 contributes to chromosome condensation and segregation, at least in part, in a manner that is distinct from the ICP-1-mediated mechanism and does not involve loading AIR-2 and condensin complexes to mitotic chromosomes. The overall structure of kinetochore is also normal accompanies with the chromosome alignment defect during metaphase in tlk-1 mutant. Moreover, the localization pattern of TLK-1 is different from the previous data and AIR-2/ICP-1 complex, which TLK-1 diffused to cytoplasm after nuclear envelope broken down. This reveals the differences in dynamic regulation and association of TLK-1 and ICP-1 towards AIR-2 in vivo. Finally, TLK-1 functions in cytokinesis by localizing AIR-2 to the midzone microtubules. Otherwise, TLK-1 may have function in chromosome architecture during chromosome condensation via phosphorylating HCP-3. And via yeast two-hybrid screen, we found a new TLK-1 interacting protein, DLC-1, which may cooperate to regulate the microtubule and kinetochore interaction during mitosis.
Subjects
tlk-1
cytokinesis
condensation
AIR-2
Aurora B
Caenorhabditis elegans
Type
thesis
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