Review The higher-order structure in the cells nucleus as the structural basis of the post-mitotic state Armando Aranda-Anzaldo * , Myrna A.R. Dent, Alejandro Martínez-Gómez Laboratorio de Biología Molecular y Neurociencias, Facultad de Medicina, Universidad Autónoma del Estado de México, PaseoTollocan y Jesús Carranza s/n, Toluca, 50180 Edo. Méx., Mexico article info Article history: Available online 18 February 2014 Keywords: Aneuploidy DNA loops DNA supercoiling Nuclear matrix Polyploidy Tensegrity abstract In metazoan cells during the interphase nuclear DNA is organized in supercoiled, topologically con- strained loops anchored to a proteinaceous compartment or substructure commonly known as the nuclear matrix (NM). The DNA-NM interactions result from a thermodynamically-driven process leading to the necessary dissipation of structural stress along chromosomal DNA, otherwise the chromosomes would break into pieces. Such DNA-NM interactions define a nuclear higher-order structure that is in- dependent of chromatin proteins. On the other hand, a metazoan cell no longer able to undergo mitosis is defined as post-mitotic and this condition indicates a terminally differentiated cell that may survive in such a state for indefinite time. The non-reversible nature of the post-mitotic state suggests a non- genetic basis for it since no spontaneous or induced mutations can revert it. Yet in individual cells the loss of proliferative potential has both a developmental and a stochastic component. Here we discuss evidence suggesting that the stability of the nuclear higher-order structure is the factor that links the stochastic and developmental components leading to the post-mitotic state. Ó 2014 Elsevier Ltd. All rights reserved. Contents 1. Introduction ....................................................................................................................... 137 2. The post-mitotic state .............................................................................................................. 139 3. Nuclear higher-order structure (NHOS) ............................................................................................... 139 3.1. A stable NHOS as the structural basis of the post-mitotic state ..................................... ............................... 140 4. The nuclear matrix in interphase ..................................................................................................... 140 4.1. The nuclear matrix and mitosis ............................................................................................... 140 5. The interphase NHOS and thermodynamics ................................................. .......................................... 142 5.1. NHOS and nuclear tensegrity .................................................................................................. 142 5.2. The NHOS and replication-induced cellular stress ................................................................................ 143 6. Polyploidy, aneuploidy and the post-mitotic state ...................................................................................... 143 7. NHOS, aneuploidy and cancer ....................................................... ................................................ 143 8. Conclusion ........................................................................................................................ 143 Conflict of interest ..................................................................................................................144 Acknowledgments ............................................................ .................................................... 144 References ........................................................................................................................ 144 1. Introduction The DNA of each metazoan chromosome is a continuous double- stranded fiber, each strand with a rigid helical backbone of phos- phodiester bonds linking millionths of nucleotides along the * Corresponding author. Tel.: þ52 722 2702899x222. E-mail addresses: aaa@uaemex.mx, armandoa10@gmail.com (A. Aranda- Anzaldo). Contents lists available at ScienceDirect Progress in Biophysics and Molecular Biology journal homepage: www.elsevier.com/locate/pbiomolbio http://dx.doi.org/10.1016/j.pbiomolbio.2014.02.002 0079-6107/Ó 2014 Elsevier Ltd. All rights reserved. Progress in Biophysics and Molecular Biology 114 (2014) 137e145