Abstract

Previous work by this group has explored some of the biochemical events that affect cell cycle G2 delay and determined how radiation affects these events. Irradiation of HeLa cells and other cells reduces levels of cyclin B1 mRNA. To determine how this occurs as well as to gain an understanding of how cyclin B1 mRNA levels are regulated in control cells, this proposal is aimed at evaluating contributions of transcription and of post transcriptional controls to cyclin B1 mRNA levels. This work will add to our knowledge of the controls regulating the transition of cells through the cell cycle and will indicate how those controls are perturbed after irradiation or treatment with DNA damaging agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047439-07
Application #
2701557
Study Section
Radiation Study Section (RAD)
Project Start
1992-05-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Zhang, Wei; Fletcher, Lynda; Muschel, Ruth J (2005) The role of Polo-like kinase 1 in the inhibition of centrosome separation after ionizing radiation. J Biol Chem 280:42994-9
Fletcher, Lynda; Yen, Tim J; Muschel, Ruth J (2003) DNA damage in HeLa cells induced arrest at a discrete point in G2 phase as defined by CENP-F localization. Radiat Res 159:604-11
Fletcher, Lynda; Cheng, Yi; Muschel, Ruth J (2002) Abolishment of the Tyr-15 inhibitory phosphorylation site on cdc2 reduces the radiation-induced G(2) delay, revealing a potential checkpoint in early mitosis. Cancer Res 62:241-50
Gupta, Anjali K; McKenna, W Gillies; Weber, Charles N et al. (2002) Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res 8:885-92
Chaudhry, M Ahmad; Chodosh, Lewis A; McKenna, W Gillies et al. (2002) Gene expression profiling of HeLa cells in G1 or G2 phases. Oncogene 21:1934-42
Gupta, A K; Bakanauskas, V J; Cerniglia, G J et al. (2001) The Ras radiation resistance pathway. Cancer Res 61:4278-82
Nair, A R; Boersma, L J; Schiltz, L et al. (2001) Paradoxical effects of trichostatin A: inhibition of NF-Y-associated histone acetyltransferase activity, phosphorylation of hGCN5 and downregulation of cyclin A and B1 mRNA. Cancer Lett 166:55-64
Janss, A J; Maity, A; Tang, C B et al. (2001) Decreased cyclin B1 expression contributes to G2 delay in human brain tumor cells after treatment with camptothecin. Neuro Oncol 3:11-21
Gupta, A K; Bernhard, E J; Bakanauskas, V J et al. (2000) RAS-Mediated radiation resistance is not linked to MAP kinase activation in two bladder carcinoma cell lines. Radiat Res 154:64-72
Kao, G D; McKenna, W G; Muschel, R J (1999) p34(Cdc2) kinase activity is excluded from the nucleus during the radiation-induced G(2) arrest in HeLa cells. J Biol Chem 274:34779-84

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