Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation

Growth and development are dependent on the faithful duplication of cells. Duplication requires accurate genome replication, the repair of any DNA dam age, and the precise segregation of chromosomes at mitosis; molecular check points ensure the proper progression and fidelity of each stage. Loss of an y of these highly conserved functions may result in genetic instability and proneness to cancer. Here we show that highly significant increases in chr omosome missegregation occur in cell lines lacking the RAD51-like genes XRC C2 and XRCC3. This increased missegregation is associated with fragmentatio n of the centrosome, a component of the mitotic spindle, and not with loss of the spindle checkpoint. Our results show that unresolved DNA damage trig gers this instability, and that XRCC2 and XRCC3 are potential tumour-suppre ssor genes in mammals.