Journal article
The cell cycle-coupled expression of topoisomerase II alpha during S phase is regulated by mRNA stability and is disrupted by heat shock or ionizing radiation
Molecular and cellular biology, Vol.16(4), pp.1500-1508
01/01/1996
DOI: 10.1128/mcb.16.4.1500
PMID: 8657123
Abstract
Topoisomerase II is a multifunctional protein required during DNA replication, chromosome disjunction at mitosis, and other DNA-related activities by virtue of its ability to alter DNA supercoiling. The enzyme is encoded by two similar but nonidentical genes: the topoisomerase II alpha and II beta genes. In HeLa cells synchronized by mitotic shake-off, topoisomerase II alpha mRNA levels were found to vary as a function of cell cycle position, being 15-fold higher in late S phase (14 to 18 h postmitosis) than during G sub(1) phase. Also detected was a corresponding increase in topoisomerase II alpha protein synthesis at 14 to 18 h postmitosis which resulted in significantly higher accumulation of the protein during S and G sub(2) phases. Topoisomerase II alpha expression was not dependent on DNA synthesis during S phase, which could be inhibited without effect on the timing or level of mRNA expression. Mechanistically, topoisomerase II alpha expression appears to be coupled to cell cycle position mainly through associated changes in mRNA stability. When cells are in S phase and mRNA levels are maximal, a half-life of greater than 4 h was observed. However, during G sub(1) phase, when cellular levels are lowest, the half-life of topoisomerase II alpha mRNA was determined to be approximately 30 min. A similar decrease in mRNA stability was also induced by two external factors known to delay cell cycle progression. Treatment of S-phase cells, at the time of maximum topoisomerase II alpha mRNA stability, with either ionizing radiation (5 Gy) or heat shock (45 degree C for 15 min) caused the accumulated topoisomerase II alpha mRNA to decay. This finding suggests a potential relationship between stress-induced decreases in topoisomerase II alpha expression and cell cycle progression delays in late S/G sub(2).
Details
- Title: Subtitle
- The cell cycle-coupled expression of topoisomerase II alpha during S phase is regulated by mRNA stability and is disrupted by heat shock or ionizing radiation
- Creators
- Prabhat C GoswamiJoseph L Roti RotiClayton R Hunt
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.16(4), pp.1500-1508
- DOI
- 10.1128/mcb.16.4.1500
- PMID
- 8657123
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 01/01/1996
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047683702771
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