[Role of hREV3 in cell cycle and proliferation].
Using a stable human kidney embryonic cell line HEK-293-M-REV3- in which the REV3 gene expression is suppressed by antisense RNA, we measured cell cycle progression and proliferation in an attempt to valuate the roles of REV3 in mutagenesis and tumorigenesis. HEK-293-M-REV3- cells were untreated or treated with DNA damaging agent UVB irradiation or methyl methanesulfonate (MMS), followed by flow cytometry and cell counting to determine the cell cycle distribution and proliferation index (PI). This study revealed that suppression of REV3 delayed spontaneous S phase progression. When treated with MMS or UVB, HEK-293-M-REV3- cells were arrested at S or G2-M phase of the cell cycle, resulting in an increased PI. In light of our previous report that suppression of REV3 limits spontaneous and DNA dam-age-induced mutagenesis, we speculate that failure in translesion synthesis due to the abolation of DNA Polymerasex may cause frequent replication fork arrest and account for the prolonged cell cycle, which is further manifested by external sources of DNA damage. Furthermore, persistent replication fork arrest may evoke cell death or apoptosis.
Xu
Fang
F
Department of Medical Genetics and Cell Biology, Ningxia Medical College, Yinchuan 750004, China. xufang@nxmc.edu.cn
Li
Yuan-Jie
YJ
D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D016372:RNA, Antisense; D008741:Methyl Methanesulfonate; D004259:DNA-Directed DNA Polymerase; C118285:REV3L protein, human