The impact of dUTPase expression on genome integrity

Horváth, A. and Batki, J. and Muha, V. and Róna, G. and Vilmos, P. and Erdélyi, M. and Vértessy G., Beáta (2013) The impact of dUTPase expression on genome integrity. FEBS Journal, 280 (Supl 1). pp. 58-59. ISSN 1742-464X

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Abstract

Accurate and stable DNA synthesis requires the precise regulation of dNTP pool. This regulation involves (i) meeting the requirements of cell cycle or DNA repair dependent DNA synthesis, (ii) the maintenance of the proper ratio of dNTP components, and (iii) the elimination of the modified nucleotides from the pool. Perturbed regulation results in the appearance of DNA lesions compromising genome integrity mostly by base excision (BER) or mismatch repair. Uracil bases are frequent lesions that can occur in DNA. dUTPase has the essential role to prevent dUMP incorporation into DNA, and an uracil DNA glycosylase, UNG, a component of BER is responsible for uracil removal from the genome. From previous observations we learned that the fruit fly lacks UNG from the three components and possess only a statio-temporal expression of dUTPase. We showed that the uracil content of DNA depends only on dUTPase expression in this organism. I also examined the transcriptional regulatory mechanism that forms dUTPase expression pattern. My results suggest that DRE motifs located in dUTPase promoter may be responsible for a cell cycle dependent expression, but there might be a DRE independent gonad-specific regulation as well. We also showed that compromising dUTPase expression in proliferating tissues causes cell autonomous tissue degradation during pupal stages. Furthermore, we showed genomic uracil accumulation, DNA fragmentation and DNA damage response activation these tissues.

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