Ž . Mutation Research 433 1999 169–181 The effect of the Saccharomyces cereÕisiae endo-exonuclease NUD1 gene expression on the resistance of HeLa cells to DNA-damaging agents Alexandre Semionov, Denis Cournoyer, Terry Y.-K. Chow ) Departments of Oncology and Medicine, Faculty of Medicine, McGill UniÕersity and Montreal General Hospital, 1650 AÕenue Cedar, Montreal, Quebec, Canada H3G 1A4. Received 28 September 1998; received in revised form 21 December 1998; accepted 8 January 1999 Abstract HeLa cells transiently transfected with a mammalian expression DNA vector expressing the Saccharomyces cereÕisiae Ž . endo-exonuclease EE NUD1 gene have exhibited changes in cell survival frequencies after treatment with different DNA-damaging agents as compared to HeLa cells transfected with a control plasmid. The NUD1-transfected cells showed a dose-dependent increase in sensitivity to UV irradiation resulting in up to 58% decrease in cell survival. In response to gamma-irradiation NUD1 transfected cells featured an increased survival at doses equal to and greater than 2.0 Gy, reaching a maximum enhancement in survival frequency of 17%. At the same time, the NUD1-transfectants featured an increase in Ž . Ž . resistance to 0.25 mM–0.5 mM cis-platin up to 58% increase in cell survival and 1.0 mM EMS 11% increase . At higher Ž concentrations of EMS NUD1 expression resulted in a decreased cell survival of the transfected cells 17% decrease for 2.5 . mM EMS . No difference in cell survival frequencies between the NUD1-transfectants and the controls was observed after treatment with different concentrations of chlorambucil and mechlorethamine. These results suggest possible roles played by EEs in different DNA repair pathways—being stimulatory for the repair of certain types of DNA lesions, such as double Ž . strand breaks DSBs , and interfering with the endogenous DNA repair systems for the repair of other types of lesions. Furthermore, these results also provide additional indirect evidence for the role of EEs in homologous recombination. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Endo-exonuclease; DNA repair; Homologous recombination; NUD1 1. Introduction In order to preserve the integrity of the genome, all living organisms from prokaryotes to mammals possess a panoply of enzymes evolved to repair ) Corresponding author. Tel.: q1-514-937-6011 ext. 4179; Fax: q1-514-937-6961 damaged DNA. Some of these enzymes are special- ized in repair of very specific types of damage such as DNA photolyase and O 6 -methylguanine-DNA w x methyltransferase 1,2 , while other repair systems are more versatile and recognize several types of DNA lesions. Among the latter there are the base excision repair system that recognizes and repairs non-bulky base adducts, reduced or fragmented bases 0921-8777r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0921-8777 99 00002-6