Chromosome condensation outside of mitosis: Mechanisms and new tools

Abstract

A basic principle of cell physiology is that chromosomes condense during mitosis. However, condensation can be uncoupled from mitotic events under certain circumstances. This phenomenon is known as ''premature chromosome condensation (PCC).'' PCC provides insights in the mechanisms of chromosome condensation, thus helping clarifying the key molecular events leading to the mitosis. Besides, PCC has proved to be an useful tool for analyzing chromosomes in interphase. For example, using PCC we can visualize genetic damage shortly after the exposure to clastogenic agents. More than 30 years ago, the first report of PCC in interphase cells fused to mitotic cells using Sendai virus was described (virus-mediated PCC). The method paved the way to a great number of fundamental discoveries in cytogenetics, radiation biology, and related fields, but it has been hampered by technical difficulties. The novel drug-induced PCC method was introduced about 10 years ago. While fusion-induced PCC exploits the action of external maturation/mitosis promoting factor (MPF), migrating from the inducer mitotic cell to the interphase recipient, drug-induced PCC exploits protein phosphatase inhibitors, which can activate endogenous intracellular MPF. This method is much simpler than fusion-induced PCC, and has already proven useful in different fields.

IBA-Europhysics Prize 2007 for ”Applied Nuclear Science and Nuclear Methods in Medicine”

“…Further details of the work of the Nuclear Physics Division can be found on our website [1]. The 2013 IBA Prize for Applied Nuclear Science and Nuclear Methods in Medicine is awarded to Prof. Marco Durante "for his outstanding and seminal contributions to research topics in the field of radiation biophysics, including work in clinical and space radiobiology, particle genetic damage and therapy, and his valuable activities in the scientific community.…”

High yields of isochromatid breaks and successive formation of chromosome exchanges may lead to reproductive cell death following high-LET irradiation

“…PCC is a very useful method and has been used widely in the cytogenetic field, particularly in radiation biology for analyzing chromosome aberration following ionizing irradiation [20,[25][26][27][28][29][30][31][32][33]. However the use of viruses or polyethylene glycol is occasionally problematic [34]. The drug-induced PCC technique has several advantages over the fusion-mediated PCC [34] and is now becoming much more popular in a wide range of cytogenetic fields [35][36][37][38][39][40][41][42][43].…”

“…However the use of viruses or polyethylene glycol is occasionally problematic [34]. The drug-induced PCC technique has several advantages over the fusion-mediated PCC [34] and is now becoming much more popular in a wide range of cytogenetic fields [35][36][37][38][39][40][41][42][43]. The drug-induced PCC method is particularly useful for analyzing the chromosomal aberrations following high-dose irradiation [35,40], which allows the chromosome aberrations to be observed immediately after the irradiation and enables the analysis of time dependent repair kinetics of chromatid break/rejoining [38,44].…”

The benzene metabolite hydroquinone enhances G2-chromosomal radiosensitivity by inducing a less-efficient G2-M-checkpoint in irradiated lymphocytes

“…This hypothesis is further supported by the results obtained when PCC was induced by means of calyculin-A, in 72-h PBL cultures after IR exposure in the presence or absence of HQ. Calyculin-A-induced PCC has been used alone or in combination with other techniques in numerous cytogenetic and biological dosimetry studies (24,27,(47)(48)(49)(50)(51). In this study, the calyculin-A induced PCC methodology was used as a novel cytokinetic tool not only for MI evaluation but also for the classification of the lymphocytes in the different phases of the cell cycle (G1, S, G2 and M-phase), as shown in Fig.…”

“…Cyclin B concentration oscillates through the cell cycle, it is very low in G1 and increases gradually from S to G2. Therefore, calyculin-A induces PCC predominantly in G2-phase followed by S-phase and only slightly in G1-phase (50). A number of late telophase post-mitotic G1 are still visible in the induced PCC but no PCC can be induced in G0 cells by means of calyculin-A alone (53), and new efforts have been recently reported to overcome this problem (54,55).…”