Figure 5.

Hypothetical routes of ring chromosome mitotic instability. Possible mechanisms of the ring “behaviour” and formation of various ring derivatives found in this study for ring chromosomes 8, 13, 18, 22 in fibroblasts and iPSC cultures. If a ring chromosome replicates without SCE (no SCE) in prophase, the ring chromatids separate equally at anaphase, resulting in normal segregation to the daughter cells. One SCE (or an odd number of SCEs) causes the two daughter chromatids to form a dicentric double-sized ring. Two SCEs (or an even number of SCEs) would result in either normal segregation or the formation of interlocked rings. Dicentric rings and interlocked rings can form anaphase bridges at cell division with subsequent possible asymmetric breakage leading to unbalanced products or chromosome non-disjunction, resulting in the production of cells without a ring/with multiple rings. When a ring chromosome undergoes anaphase lagging, a micronucleus can form with either subsequent loss (resulting in monosomy) or reunion and chromothripsis (resulting in multiple rearrangements). As a result, numerical aberrations, microstructural rearrangements or normal segregation can be found. Obviously, combinations of different events can occur in a single cell line (and even in a single cell), so we present the names of the cell lines at the positions where the effect is observed more frequently. Dashed line arrows: passage to the next cell cycle.