Crisis-associated HR may also project instability away from telomeres if it stimulates interactions between dispersed, repetitive sequences such as Alu elements. Such events have been observed to generate deletions and translocations associated with cancer. Recent discoveries have suggested that telomerase may have effects on global genome stability, particularly with regard to responses to DNA double-strand breaks. In particular,SB431542 telomerase-deficient mice display hypersensitivity to ionizing radiation and delays in DSB repair that may reflect a defect in HR. While it remains unclear if the effect of telomerase on DSB repair is direct or indirect, these results suggest that telomerase may affect the generation of tumorigenic genome rearrangements. In this manuscript we describe the effect of the loss of telomerase on the formation of chromosomal translocations by HR in budding yeast. We observed a crisis-associated increase in the rate of spontaneous translocation when one of the substrates was located near a telomere that was similar to increases in the rate of mutation and interhomolog recombination observed previously at this and other loci. This is consistent with the gathering evidence for a substantial increase in genome instability concomitant with crisis. In addition to these crisis-associated effects we have also shown that loss of telomerase results in decreased frequencies of translocation following DSB formation adjacent to the translocation substrates,SCH727965 before, during and after crisis. This defect in DSB repair reflects a constitutive sequestra-tion of the central HR protein, Rad52, at telomeres, and a decrease in its recruitment to DSBs, suggesting that telomerase exerts an indirect effect on global genome stability. These results suggest that the resumption of telomerase function in pre-malignant cells could stimulate genome rearrangement that may contribute to the progression toward tumor formation in humans. In aging mice and human cells lacking telomerase, the formation of translocations has been observed in response to telomere dysfunction during crisis, and is thought to be involved in carcinogenesis.