Host: The Japan Radiation Research Society
Hypersensitivity to DNA damaging agents and chromosomal aberration including numerical chromosomal abnormality are found in cells with mutated homologous recombination (HR) proteins. Numerical chromosomal abnormalities are generally classified into aneuploidy and polyploidy, both of which are assumed to be critical condition, as they are observed frequently in cancer cells. Rad51 paralogs share sequence homology to Rad51, a central player of HR. They have been shown to play roles in HR in chicken DT40 and rodent CHO cells. We generated human HCT116 cell lines with mutated Rad51 paralogs by gene targeting; Rad51B+/-/-/-, Rad51C+/-/-/- and XRCC3-/- cells. Human Rad51 paralogs are shown to play a role in HR in HCT116 cells, since the mutants showed hypersensitivity to MMC and decreases in sister chromatid exchange. Interestingly, numerical chromosomal abnormalities were increased in these cell lines. Tetraploidy was increased in XRCC3-/-, while aneuploidy was increased in Rad51B+/-/-/- and Rad51C+/-/-/-. In addition, centrosome fragmentation and slow growth caused by cell cycle checkpoint activation were observed in Rad51B+/-/-/- and Rad51C+/-/-/-. We will discuss the mechanism of the development of polyploidy and aneuploidy in these cells.
