The role of meiotic cohesin REC8 in chromosome segregation in gamma irradiation-induced endopolyploid tumour cells.
Escape from mitotic catastrophe and generation of endopolyploid tumour cells (ETCs) represents a potential survival strategy of tumour cells in response to genotoxic treatments. ETCs that resume the mitotic cell cycle have reduced ploidy and are often resistant to these treatments. In search for a mechanism for genome reduction, we previously observed that ETCs express meiotic proteins among which REC8 (a meiotic cohesin component) is of particular interest, since it favours reductional cell division in meiosis. In the present investigation, we induced endopolyploidy in p53-dysfunctional human tumour cell lines (Namalwa, WI-L2-NS, HeLa) by gamma irradiation, and analysed the sub-cellular localisation of REC8 in the resulting ETCs. We observed by RT-PCR and Western blot that REC8 is constitutively expressed in these tumour cells, along with SGOL1 and SGOL2, and that REC8 becomes modified after irradiation. REC8 localised to paired sister centromeres in ETCs, the former co-segregating to opposite poles. Furthermore, REC8 localised to the centrosome of interphase ETCs and to the astral poles in anaphase cells where it colocalised with the microtubule-associated protein NuMA. Altogether, our observations indicate that radiation-induced ETCs express features of meiotic cell divisions and that these may facilitate chromosome segregation and genome reduction.
Erenpreisa
Jekaterina
J
Latvian Biomedicine Research and Study Centre, Riga, Latvia.
Cragg
Mark S
MS
Salmina
Kristine
K
Hausmann
Michael
M
Scherthan
Harry
H
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000502:physiology / Q000528:radiation effects; D002503:Centromere / Q000378:metabolism; D020090:Chromosome Segregation / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D011123:Polyploidy; D034622:RNA Interference; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism
D018797:Cell Cycle Proteins; C507675:REC8 protein, human; C496644:SGO1 protein, human; C510590:SGO2 protein, human; D051135:Rad51 Recombinase