Armakolas and Klar explored the hypothesis that the factors influencing DNA strand segregation might be the same as those affecting left-right body axis formation. They focused on the gene encoding the left-right dynein motor protein (LRD), which, when mutated, causes left-right axis randomization in some internal organs. Using an Hprt-recombination experimental system, they found that reducing LRD expression by RNA interference led to nearly random chromatid segregation in cell lines that were initially exclusively X or Z type. This segregation ratio (2.1 to 3.1 X:Z) was similar to that observed in cell lines not normally expressing LRD and in other embryonic stem cell lines. The authors proposed two possible mechanisms for LRD's role: eliminating Hprt-recombination at different stages of the cell cycle in different cell types, or directly affecting the orientation of joined homologs on the spindle. The presence of LRD led to exclusive X or Z segregation, but the exact mechanism remains unclear. Despite the complexity, Armakolas and Klar's experiment is commended for its innovative approach to an unorthodox hypothesis.Armakolas and Klar explored the hypothesis that the factors influencing DNA strand segregation might be the same as those affecting left-right body axis formation. They focused on the gene encoding the left-right dynein motor protein (LRD), which, when mutated, causes left-right axis randomization in some internal organs. Using an Hprt-recombination experimental system, they found that reducing LRD expression by RNA interference led to nearly random chromatid segregation in cell lines that were initially exclusively X or Z type. This segregation ratio (2.1 to 3.1 X:Z) was similar to that observed in cell lines not normally expressing LRD and in other embryonic stem cell lines. The authors proposed two possible mechanisms for LRD's role: eliminating Hprt-recombination at different stages of the cell cycle in different cell types, or directly affecting the orientation of joined homologs on the spindle. The presence of LRD led to exclusive X or Z segregation, but the exact mechanism remains unclear. Despite the complexity, Armakolas and Klar's experiment is commended for its innovative approach to an unorthodox hypothesis.