This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guillet, M. Articles by Boiteux, S. Search for Related Content PubMed PubMed Citation Articles by Guillet, M. Articles by Boiteux, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2003, p. 8386-8394, Vol. 23, No. 22
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.22.8386-8394.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Origin of Endogenous DNA Abasic Sites in Saccharomyces cerevisiae

CEA, DSV, Département de Radiobiologie et Radiopathologie, UMR 217 CNRS/CEA Radiobiologie Moléculaire et Cellulaire, F-92265 Fontenay aux Roses, France

Received 21 March 2003/ Returned for modification 2 May 2003/ Accepted 4 August 2003

Abasic (AP) sites are among the most frequent endogenous lesions in DNA and present a strong block to replication. In Saccharomyces cerevisiae, an apn1 apn2 rad1 triple mutant is inviable because of its incapacity to repair AP sites and related 3'-blocked single-strand breaks (M. Guillet and S. Boiteux, EMBO J. 21:2833, 2002). Here, we investigated the origin of endogenous AP sites in yeast. Our results show that the deletion of the UNG1 gene encoding the uracil DNA glycosylase suppresses the lethality of the apn1 apn2 rad1 mutant. In contrast, inactivation of the MAG1, OGG1, or NTG1 and NTG2 genes encoding DNA glycosylases involved in the repair of alkylation or oxidation damages does not suppress lethality. Although viable, the apn1 apn2 rad1 ung1 mutant presents growth delay due to a G₂/M checkpoint. These results point to uracil as a critical source of the formation of endogenous AP sites in DNA. Uracil can arise in DNA by cytosine deamination or by the incorporation of dUMP during replication. Here, we show that the overexpression of the DUT1 gene encoding the dUTP pyrophosphatase (Dut1) suppresses the lethality of the apn1 apn2 rad1 mutant. Therefore, this result points to the dUTP pool as an important source of the formation of endogenous AP sites in eukaryotes.

This article has been cited by other articles:

• Pettersen, H. S., Sundheim, O., Gilljam, K. M., Slupphaug, G., Krokan, H. E., Kavli, B. (2007). Uracil-DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of base excision repair by distinct mechanisms. Nucleic Acids Res 35: 3879-3892 [Abstract] [Full Text]  
• Ragu, S., Faye, G., Iraqui, I., Masurel-Heneman, A., Kolodner, R. D., Huang, M.-E. (2007). Oxygen metabolism and reactive oxygen species cause chromosomal rearrangements and cell death. Proc. Natl. Acad. Sci. USA 104: 9747-9752 [Abstract] [Full Text]  
• Lu, C.-C., Huang, H.-T., Wang, J.-T., Slupphaug, G., Li, T.-K., Wu, M.-C., Chen, Y.-C., Lee, C.-P., Chen, M.-R. (2007). Characterization of the Uracil-DNA Glycosylase Activity of Epstein-Barr Virus BKRF3 and Its Role in Lytic Viral DNA Replication. J. Virol. 81: 1195-1208 [Abstract] [Full Text]  
• Guillet, M., Van Der Kemp, P. A., Boiteux, S. (2006). dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae.. Nucleic Acids Res 34: 2056-2066 [Abstract] [Full Text]  
• Auerbach, P., Bennett, R. A. O., Bailey, E. A., Krokan, H. E., Demple, B. (2005). Mutagenic specificity of endogenously generated abasic sites in Saccharomyces cerevisiae chromosomal DNA. Proc. Natl. Acad. Sci. USA 102: 17711-17716 [Abstract] [Full Text]  
• Izumi, T., Brown, D. B., Naidu, C. V., Bhakat, K. K., MacInnes, M. A., Saito, H., Chen, D. J., Mitra, S. (2005). Two essential but distinct functions of the mammalian abasic endonuclease. Proc. Natl. Acad. Sci. USA 102: 5739-5743 [Abstract] [Full Text]  
• Karumbati, A. S., Wilson, T. E. (2005). Abrogation of the Chk1-Pds1 Checkpoint Leads to Tolerance of Persistent Single-Strand Breaks in Saccharomyces cerevisiae. Genetics 169: 1833-1844 [Abstract] [Full Text]  
• Andersen, S., Heine, T., Sneve, R., Konig, I., Krokan, H. E., Epe, B., Nilsen, H. (2005). Incorporation of dUMP into DNA is a major source of spontaneous DNA damage, while excision of uracil is not required for cytotoxicity of fluoropyrimidines in mouse embryonic fibroblasts. Carcinogenesis 26: 547-555 [Abstract] [Full Text]  
• Ide, Y., Tsuchimoto, D., Tominaga, Y., Nakashima, M., Watanabe, T., Sakumi, K., Ohno, M., Nakabeppu, Y. (2004). Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice. Blood 104: 4097-4103 [Abstract] [Full Text]  
• Cabelof, D. C., Raffoul, J. J., Nakamura, J., Kapoor, D., Abdalla, H., Heydari, A. R. (2004). Imbalanced Base Excision Repair in Response to Folate Deficiency Is Accelerated by Polymerase {beta} Haploinsufficiency. J. Biol. Chem. 279: 36504-36513 [Abstract] [Full Text]