The Influence of FEN-1 Gene on
Cell Cycle and Genetic Stability
SHI Bin-Shan,
YU Ying-Nian*, CAI Zhu-Nan
( Department of Pathophysiology, School of Medicine, Zhejiang University,
Hangzhou 310031, China )
SHEN Bin-Hui
( City of Hope National Medical Center and Beckman Research Institute,
Duart, CA91010-3000 USA )
Abstract FEN-1 is
essential in the cell replication, repair and in the maintenance of cellular
genetic stability. In this report, it was verfied that FEN-1 antisense
mRNA fragment was expressed in the cell line FL-FEN-1–,constructed
in our lab, blocking FEN-1 gene expression. It was found by the flow
cytometer analysis that the cell cycle of FL-FEN-1– cells was
delayed in the S-phase DNA synthesis process and arrested in G1
phase. In a mutation assay, based on the shuttle-plasmid pZ189, the spontaneous
mutation frequency of SupF tRNA gene in the plasmid in the FL-FEN-1–
cells was 19.1×104,while it was 2.9×104 and 3.0×104
in the control cells FL and FL-M, respectively. Further study showed that
nontargeted mutation frequency of the FL-FEN-1– cell induced by MNNG
was almost the same as the control, indicating that the mutants derived from
the block of FEN-1 gene and the nontargeted mutants may be formed
through different passways. The FL-FEN-1– cells exhibit increased
sensitivity to alkylating agent MNNG.
Key words cell cycle； genetic instability； nontargeted mutation； MNNG sensitivity
*Corresponding author： Tel/Fax, 86-571-7217149； e-mail, [email protected]