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Trp53-dependent DNA-repair is affected by the codon 72 polymorphism

Oncogene volume 25, pages 3489–3500 (2006)Cite this article

Abstract

Trp53 is arguably the most critical tumour suppressor gene product that inhibits malignant transformation. Besides mutations that inactivate Trp53 functions, genetic polymorphisms have been suggested to be risk factors for cancer. A polymorphic site at codon 72 in exon 4 encodes either an arginine amino acid (Trp5372R) or a proline residue (Trp5372P). Previous studies have shown that the Trp5372R form is more efficient in apoptosis induction, whereas the Trp5372P form was suggested to induce G1 arrest better. Here we report that Trp5372P is more efficient than Trp5372R in specifically activating several Trp53-dependent DNA-repair target genes in several cellular systems. Moreover, using isogenic cell lines and several DNA-repair assays, we show that Trp5372P cells have a significantly higher DNA-repair capacity than the Trp5372R cells. Furthermore, Trp5372P-expressing cells exhibit reduced micronuclei formation compared to Trp5372R-expressing cells, suggesting that genomic instability is reduced in these cells. Together, the data highlight the functional differences between the Trp53 polymorphic variants, and suggest that their expression status may influence cancer risk.

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Acknowledgements

We thank Dr P Hande for advise and help with micronuclei analysis and Drs H Arakawa and D Gupta for plasmids and cell lines. We thank the National Medical Research Council, Singapore, for their generous funding and support to KS.

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  1. Laboratory of Molecular Carcinogenesis, National Cancer Centre, Singapore

    M Siddique & K Sabapathy

  2. Department of Biochemistry, National University of Singapore, Singapore

    K Sabapathy

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  1. M Siddique
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Correspondence to K Sabapathy.

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Siddique, M., Sabapathy, K. Trp53-dependent DNA-repair is affected by the codon 72 polymorphism. Oncogene 25, 3489–3500 (2006). https://doi.org/10.1038/sj.onc.1209405

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