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dNTP Supply Gene Expression Patterns after P53 Loss
Departments of Epidemiology and Biostatistics, General Medical Sciences (Oncology), and Pathology, Case Western Reserve School of Medicine, Cleveland, OH 44106, USA
Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Ave. R40, Cleveland, OH 44195, USA
Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH 44106, USA
* Author to whom correspondence should be addressed.
Received: 27 October 2012; in revised form: 27 October 2012 / Accepted: 15 November 2012 / Published: 20 November 2012
Abstract: Loss of the transcription factor p53 implies mRNA losses of target genes such as the p53R2 subunit of human ribonucleotide reductase (RNR). We hypothesized that other genes in the dNTP supply system would compensate for such p53R2 losses and looked for this in our own data and in data of the Gene Expression Omnibus (GEO). We found that the de novo dNTP supply system compensates for p53R2 losses with increases in RNR subunit R1, R2, or both. We also found compensatory increases in cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) and in mitochondrial deoxyguanosine kinase (dGK), all of the salvage dNTP supply system; in contrast, the remaining mitochondrial salvage enzyme thymidine kinase 2 (TK2) decreased with p53 loss. Thus, TK2 may be more dedicated to meeting mitochondrial dNTP demands than dGK which may be more obligated to assist cytosolic dNTP supply in meeting nuclear DNA dNTP demands.
Keywords: p53; Li-Fraumeni; ribonucleotide reductase; p53R2; dNTP supply and demand; gene expression; thymidine kinase; deoxyguanosine kinase; deoxycytidine kinase
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MDPI and ACS Style
Radivoyevitch, T.; Saunthararajah, Y.; Pink, J.; Ferris, G.; Lent, I.; Jackson, M.; Junk, D.; Kunos, C.A. dNTP Supply Gene Expression Patterns after P53 Loss. Cancers 2012, 4, 1212-1224.
Radivoyevitch T, Saunthararajah Y, Pink J, Ferris G, Lent I, Jackson M, Junk D, Kunos CA. dNTP Supply Gene Expression Patterns after P53 Loss. Cancers. 2012; 4(4):1212-1224.
Radivoyevitch, Tomas; Saunthararajah, Yogen; Pink, John; Ferris, Gina; Lent, Ian; Jackson, Mark; Junk, Damian; Kunos, Charles A. 2012. "dNTP Supply Gene Expression Patterns after P53 Loss." Cancers 4, no. 4: 1212-1224.