Telomere replication: poised but puzzling

Faithful replication of chromosomes is essential for maintaining genome stability. Telomeres, the chromosomal termini, pose quite a challenge to replication machinery due to the complexity in their structures and sequences. Efficient and complete replication of chromosomes is critical to prevent aberrant telomeres as well as to avoid unnecessary loss of telomere DNA. Compelling evidence supports the emerging picture of synergistic actions between DNA replication proteins and telomere protective components in telomere synthesis. This review discusses the actions of various replication and telomere-specific binding proteins that ensure accurate telomere replication and their roles in telomere maintenance and protection.     

Studies on structure activity relationship of some dihydroxy-4-methylcoumarin antioxidants based on their interaction with Fe(III) and ADP

Three dihydroxy-4-methylcoumarin (DHMC) derivatives, namely 7,8-DHMC, 6,7-DHMC and 5,7-DHMC alone and complexed with Fe (III) and ADP have been tested for their antioxidative potential. Chemical speciation studies and formation constants reveal the formation of strong DHMC–Fe–ADP (1:1:1) ternary complex. In vitro studies were done for their antioxidative property by scavenging the superoxide radicals (O ₂ ^– ) generated by xanthine + xanthine oxidase (XO) reaction. The IC₅₀ values for 7,8-DHMC, 6,7-DHMC and 5,7-DHMC and their ternary complexes with Fe (III)–ADP worked out to be 34.0 M, 62.0 M, 8.80 mM and 10.5, 11.5 and 148.5 M, respectively. The results indicate that O ₂ ^– scavenging potential of all the three DHMCs increased significantly after forming the ternary complex with Fe(III) and ADP. The structure activity relationship studies suggest that the introduction of hydroxyl group at 7th and 8th positions in the coumarins, irrespective of Fe(III)–ADP complexation, increases the antioxidative efficacy. No change in uric acid production in the reactions done for all studies further reveals that the coumarin derivatives and their complexes were the only causative factors for O ₂ ^– scavenging and not the suppression of the enzyme, xanthine oxidase.Published online: March 2005     

Ornithine decarboxylase-antizyme is rapidly degraded through a mechanism that requires functional ubiquitin-dependent proteolytic activity.

Antizyme is a polyamine-induced cellular protein that binds to ornithine decarboxylase (ODC), and targets it to rapid ubiquitin-independent degradation by the 26S proteasome. However, the metabolic fate of antizyme is not clear. We have tested the stability of antizyme in mammalian cells. In contrast with previous studies demonstrating stability in vitro in a reticulocyte lysate-based degradation system, in cells antizyme is rapidly degraded and this degradation is inhibited by specific proteasome inhibitors. While the degradation of ODC is stimulated by the presence of cotransfected antizyme, degradation of antizyme seems to be independent of ODC, suggesting that antizyme degradation does not occur while presenting ODC to the 26S proteasome. Interestingly, both species of antizyme, which represent initiation at two in-frame initiation codons, are rapidly degraded. The degradation of both antizyme proteins is inhibited in ts20 cells containing a thermosensitive ubiquitin-activating enzyme, E1. Therefore we conclude that in contrast with ubiquitin-independent degradation of ODC, degradation of antizyme requires a functional ubiquitin system.