Cortés Felipe, Mateos Santiago, Pastor Nuria, Domínguez Inmaculada
Department of Cell Biology, Faculty of Biology of Seville, Avenue Reina Mercedes 6, E-41012 Seville, Spain.
Life Sci. 2004 Nov 26;76(2):121-35. doi: 10.1016/j.lfs.2004.08.006.
Both the biological significance and the molecular mechanism of endoreduplication (END) have been debated for a long time by cytogeneticists and researchers into cell cycle enzymology and dynamics alike. Mainly due to the fact that a wide variety of agents have been reported as able to induce endoreduplication and the diversity of cell types where it has been described, until now no clear or unique mechanism of induction of this phenomenon, rare in animals but otherwise quite common in plants, has been proposed. DNA topoisomerase II (topo II), plays a major role in mitotic chromosome segregation after DNA replication. The classical topo II poisons act by stabilizing the enzyme in the so-called cleavable complex and result in DNA damage as well as END, while the true catalytic inhibitors, which are not cleavable-complex-stabilizers, do induce END without concomitant DNA and chromosome damage. Taking into account these observations on the induction of END by drugs that interfere with topo II, together with our recently obtained evidence that the nature of DNA plays an important role for chromosome segregation [Cortes, F., Pastor, N., Mateos, S., Dominguez, I., 2003. The nature of DNA plays a role in chromosome segregation: endoreduplication in halogen-substituted chromosomes. DNA Repair 2, 719-726.], a straightforward model is proposed in which the different mechanisms leading to induced END are considered.
核内复制（END）的生物学意义和分子机制长期以来一直受到细胞遗传学家以及细胞周期酶学和动力学研究人员的争论。主要由于以下事实：已报道多种因子能够诱导核内复制，并且其在已被描述的细胞类型中具有多样性，直到现在，尚未提出关于这种在动物中罕见但在植物中相当常见的现象的明确或独特的诱导机制。DNA拓扑异构酶II（topo II）在DNA复制后的有丝分裂染色体分离中起主要作用。经典的topo II毒药通过在所谓的可切割复合物中稳定该酶而起作用，并导致DNA损伤以及核内复制，而真正的催化抑制剂，即不是可切割复合物稳定剂的那些，确实诱导核内复制而不伴随DNA和染色体损伤。考虑到这些关于干扰topo II的药物诱导核内复制的观察结果，以及我们最近获得的证据，即DNA的性质对染色体分离起重要作用[Cortes, F., Pastor, N., Mateos, S., Dominguez, I., 2003. DNA的性质在染色体分离中起作用：卤素取代染色体中的核内复制。DNA修复2, 719 - 726。]，提出了一个简单的模型，其中考虑了导致诱导核内复制的不同机制。
