Serrano Diego, D'Amours Damien
Département de Pathologie et Biologie Cellulaire, Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Succursale Centre-Ville, Montreal, QC H3C 3J7 Canada.
Syst Synth Biol. 2014 Sep;8(3):195-203. doi: 10.1007/s11693-014-9151-9. Epub 2014 Jul 27.
The drive to proliferate and the need to maintain genome integrity are two of the most powerful forces acting on biological systems. When these forces enter in conflict, such as in the case of cells experiencing DNA damage, feedback mechanisms are activated to ensure that cellular proliferation is stopped and no further damage is introduced while cells repair their chromosomal lesions. In this circumstance, the DNA damage response dominates over the biological drive to proliferate, and may even result in programmed cell death if the damage cannot be repaired efficiently. Interestingly, the drive to proliferate can under specific conditions overcome the DNA damage response and lead to a reactivation of the proliferative program in checkpoint-arrested cells. This phenomenon is known as adaptation to DNA damage and is observed in all eukaryotic species where the process has been studied, including normal and cancer cells in humans. Polo-like kinases (PLKs) are critical regulators of the adaptation response to DNA damage and they play key roles at the interface of cell cycle and checkpoint-related decisions in cells. Here, we review recent progress in defining the specific roles of PLKs in the adaptation process and how this conserved family of eukaryotic kinases can integrate the fundamental need to preserve genomic integrity with effective cellular proliferation.
细胞增殖的驱动力和维持基因组完整性的需求是作用于生物系统的两种最强大的力量。当这些力量发生冲突时，比如细胞遭遇DNA损伤的情况，反馈机制就会被激活，以确保细胞增殖停止，并且在细胞修复其染色体损伤时不会引入进一步的损伤。在这种情况下，DNA损伤反应压倒了细胞增殖的生物学驱动力，如果损伤无法有效修复，甚至可能导致程序性细胞死亡。有趣的是，在特定条件下，增殖驱动力能够克服DNA损伤反应，并导致处于检查点阻滞状态的细胞重新激活增殖程序。这种现象被称为对DNA损伤的适应性，在所有已研究该过程的真核生物物种中都能观察到，包括人类的正常细胞和癌细胞。Polo样激酶（PLKs）是对DNA损伤适应性反应的关键调节因子，它们在细胞周期和细胞内检查点相关决策的界面发挥关键作用。在此，我们综述了在确定PLKs在适应性过程中的具体作用以及这个保守的真核激酶家族如何将维护基因组完整性的基本需求与有效的细胞增殖整合方面的最新进展。
