Topoisomerases covalent modification

DNA topoisomerases have been found to be subject to covalent modifications that modulate their DNA-relaxing activities. An example of this is the ADP-ribosylation of calf thymus topoisomerase I by poly(ADP-ribose) synthetase (Ferro et al., 1983 Jongstra-Bilen et al., 1983 Ferro and Olivera, 1984). The modified enzyme is less active in DNA relaxation. The possibility that topoisomerase I and poly(ADP-ribose) synthetase are associated in vivo was suggested by the observation that they copurify (Ferro et al., 1983 Jongstra-Bilen et al., 1983). 

The cellular functions of topoisomerases demand much more attention, particularly in higher eucaryotes where little is known about their biological role. Tantalizing clues have come from their proposed involvement in chromosome structure and transcription complexes, and from demonstrations that their activities can be modulated by covalent modification. These aspects remain to be fully explored. 

In eukaryotes, DNA supercoiling is an essential step in forming the DNA histone complexes of chromatin, and thus, in organizing the chromosome. DNA supercoiUng is controlled by a class of enzymes called topoisomerases [22]. We could demonstrate that the topoisomerase I molecule may be a target for ADP-ribosylation and that this covalent modification inactivates this enzyme involved in chromosome organization [23]. 

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