Mechanism of G2-Repair to preserve chromosome integrity and its inhibition by caffeine

Abstract

[EN] In proliferating eukaryotic cells, there occurs a striking chromosome repair mechanism, wich operates during G2 and prophase of the division cycle. The main task of this repair mechanism could by the removal of DNA lesions able to give rise chromosomal aberrations during chromatin condensation and chromosome movements in next mitosis. In the present work, we study this repair mechanism, its inhibition by caffeine and we propose a model to explain the estrategy of cell mechanism operating under control conditions and after the treatment with any clastogenic agent. The G2-prophase repair is a mechanism of eukaryotic cells reminiscent of bacterial SOS system and it would operate as follows: I) The response is induced by the presence of certain DNA lesions in post-replicative and premiotic genome, whenever they were induced. Under these circumstances, a cell cycle arrest takes place in G2, also termed division delay. II) During the G2 arrest, DNA repair pathways operate to restore DNA structure. III) When adequate DNA structure for physical chromosome integrity is achieved cells go into mitosis. This recovery from arrest is dependent on protein synthesis. Caffeine is an inhibitor of G2-prophase repair mechanism by cancelling division delay and, probably, by affecting the rate of DNA repair at the same time. Caffeine efficiency appears to by dependent on drug concentration and cellular ATP level. The lower the level the higher its inhibitory efficiency. Cycloheximide can ameliorate DNA repair during G2-prophase, even in the presence of caffeine. Likely, inhibition of protein synthesis during post-treatments with damaging agents allows damaged cells to have enough time for DNA repair before mitosis.