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When genome integrity and cell cycle decisions collide: roles of polo kinases in cellular adaptation to DNA damage

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Systems and Synthetic Biology

Abstract

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.

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Acknowledgments

We thank Julie St-Pierre and members of the D’Amours laboratory for their comments on the manuscript. Research in D.D.’s laboratory is supported by the Cancer Research Society and by the Canadian Institutes of Health Research (MOP 82912). D.D. is a recipient of a Tier II Canada Research Chair in Cell Cycle Regulation and Genomic Integrity. D.S. is supported by a postdoctoral fellowship from the FRQS.

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  1. 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

    Diego Serrano & Damien D’Amours

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  1. Diego Serrano
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  2. Damien D’Amours
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Correspondence to Damien D’Amours.

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Serrano, D., D’Amours, D. When genome integrity and cell cycle decisions collide: roles of polo kinases in cellular adaptation to DNA damage. Syst Synth Biol 8, 195–203 (2014). https://doi.org/10.1007/s11693-014-9151-9

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