DNA-repair mechanisms : symposium, Schloss Reinhartshausen/Rhein, Oct. 4th/5th, 1971 / chairman H. Altmann.

Date:
[1972]
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Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: DNA-repair mechanisms : symposium, Schloss Reinhartshausen/Rhein, Oct. 4th/5th, 1971 / chairman H. Altmann. Source: Wellcome Collection.

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    whether hydroxyurea inhibits ligase activity in vitro ; our data [Coyle, M. and B. Strauss: Cancer Res. 30: 2314 (1970)] and the data I mentioned yester day published by Ben-Hur and Ben-Ishai [Photochem. Photobiol. 13: 337 (1971)] indicate that it can inhibit the joining of breaks in vivo. Boyle: Are you talking about mammalian systems or bacteria? Strauss: About mammalian systems. Ben-Hur and Ben-Ishai studied breaks occurring as a result of the repair of UV-induced damage. In our own work [Coyle, M. and B. Strauss : Cancer Res. 30: 2314 (1970)] it appeared that newly synthesized DNA formed in the presence of hydroxyurea was not joined to larger fragments. Regan : We have hydroxyurea present at 3 x 10 -3 M in our UV experiments and in our gamma experiments. There is no inhibition of UV repair or gamma repair by this compound. Strauss: By this sucrose gradient method? Regan: The BU insertion and photolysis method. I mean hydroxyurea does not inhibit the shift back to higher molecular weight after gamma irra diation. Painter: I think it is a very strong point on the Ben-Hur and Ben-Ishai paper that nobody else doing sucrose gradients has got even close to these results. I mean not even close. You look after UV and you don’t see anything like that. Strauss : Hydroxyurea has been reported to induce chromosome breaks [Yu, C. and W. Sinclair: J. Cell Physiol. 72: 39 (1968)]. We have also ob served the degradation of the DNA of HEp.2 cells incubated in the presence of hydroxyurea. This degradation can be observed on alkaline sucrose gradients and also by the Hirt [J. molec. Biol. 26: 365-369 (1967)] technique. We sup posed, as an explanation for this degradation, that over the long term there is some inhibition of a joining process by hydroxyurea. Now I am sorry to have brought in the paper by Ben-Hur and Ben-Ishai because the authors are not here to discuss their work. However, I did quote it because their results sup port the ideas we derive from the experiments I have just described.