- 作者: Hsing-Hsi Li; Chuen-Sheue Chiang; Hsiao-Yu Huang; Gwo-Jen Liaw
- 作者服務機構: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan, Republic of China
- 中文摘要: --
- 英文摘要:
Background :
High levels of Hepatoma Up-Regulated Protein (HURP) and Tousled-Like
Kinase (TLK) transcripts are found in hepatocellular carcinoma. HURP
overexpression induces anchorage-independent growth of 293-T cells and enhances a
rough-eye phenotype resulting from tlk overexpression in Drosophila. In addition,
both HURP and Mars, a Drosophila HURP sequence homologue, promote
polymerization of mitotic spindles. Thus, the genetic interaction of mars with tlk
might be required for accurate chromosome segregation.
Methods :
To reveal whether chromosome fidelity was decreased, the frequency of
gynandromorphy, an individual with both male and female characteristics, and of
non-disjunction were measured in the progeny from parents with reduced mars and/or
tlk activities and analyzed by Student’s t-test. To show that the genetic interaction
between mars and tlk is epistatic or parallel, a cytological analysis of embryos with
either reduced or increased activities of mars and/or tlk was used to reveal defects in
mitotic-spindle morphology and chromosome segregation.
Results :
A significant but small fraction of the progeny from parents with reduced mars
activity showed gynandromorphy and non-disjunction. Results of cytological analysis
revealed that the decrease in chromosome fidelity was a result of delayed
polymerization of the mitotic spindle, which led to asynchronous chromosome
segregation in embryos that had reduced mars activity. By removing one copy of
tousled-like kinase (tlk) from flies with reduced mars activity, chromosome fidelity
was further reduced. This was indicated by an increased in the non-disjunction rate
and more severe asynchrony. However, the morphology of the mitotic spindles in the
embryos at metaphase where both gene activities were reduced was similar to that in
mars embryos. Furthermore, tlk overexpression did not affect the morphology of the
mitotic spindles and the cellular localization of Mars protein.
Conclusions :
Chromosome fidelity in progeny from parents with reduced mars and/or tlk
activity was impaired. The results from cytological studies revealed that mars and tlk
function in parallel and that a balance between mars activity and tlk activity is
required for cells to progress through mitosis correctly, thus ensuring chromosome
fidelity. - 中文關鍵字: --
- 英文關鍵字: --