- 作者: Voon-Kwan Siew; Chang-Yih Duh; Shang-Kwei Wang
- 作者服務機構: Department of Microbiology, Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in
infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs
to a conserved protein family from herpesviruses. Some reported roles among UL76 family
members include involvement in virulence determination, lytic replication, reactivation of latent
virus, modulation of gene expression, induction of apoptosis, and perturbation of cell cycle
progression, as well as potential nuclease activity. Previously, we have shown that stable expression
of UL76 inhibits HCMV replication in glioblastoma cells.
Methods: To examine chromosomal integrity and the DNA damage signal γ-H2AX in cells
constitutively expressing UL76, immunofluorescent cell staining and Western blotting were
performed. The comet assay was employed to assess DNA breaks in cells transiently expressing
UL76.
Results: We report that stably transfected cells expressing UL76 developed chromosome
aberrations including micronuclei and misaligned chromosomes, lagging and bridging. In mitotic
cells expressing UL76, aberrant spindles were increased compared to control cells. However, cells
with supernumerary centrosomes were marginally increased in UL76-expressing cells relative to
control cells. We further demonstrated that UL76-expressing cells activated the DNA damage
signal γ-H2AX and caused foci formation in nuclei. In addition, the number of cells with DNA
breaks increased in proportion to UL76 protein levels.
Conclusion: Our findings suggest that the virus-associated protein UL76 induces DNA damage
and the accumulation of chromosome aberrations. - 中文關鍵字: --
- 英文關鍵字: --