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The structure-specific nuclease, Rad27p/FEN1, plays a crucial role in DNA repair and replication mechanisms in the nucleus. Genetic assays using the mutant have shown altered rates of DNA recombination, microsatellite instability, and point mutation in mitochondria. In this study, we examined the role of Rad27p in mitochondrial mutagenesis and double-strand break (DSB) repair in Our findings show that Rad27p is essential for efficient mitochondrial DSB repair by a pathway that generates deletions at a region flanked by direct repeat sequences. Mutant analysis suggests that both exonuclease and endonuclease activities of Rad27p are required for its role in mitochondrial DSB repair. In addition, we found that the nuclease activities of Rad27p are required for the prevention of mitochondrial DNA (mtDNA) point mutations, and in the generation of spontaneous mtDNA rearrangements. Overall, our findings underscore the importance of Rad27p in the maintenance of mtDNA, and demonstrate that it participates in multiple DNA repair pathways in mitochondria, unlinked to nuclear phenotypes.

Background: Metastatic prostate cancer is incurable, but systemic therapies can improve quality of life and prolong survival. Accurate perceptions of treatment risks and benefits are vital as patients with metastatic disease make treatment decisions.We assessed treatment-related expectations for benefit among patients with metastatic prostate cancer and explored associated sociodemographic characteristics. Methods: Men with metastatic prostate cancer (N = 100) completed surveys assessing their treatment-related expectations for cancer cure, symptom relief, and prolonged life expectancy. Frequencies were used to describe the proportions of reported expectations. Fisher's exact tests were used to assess the associations of sociodemographic characteristics with treatment expectations. Results: One third (33%) of participants believed treatment was at least a little likely to cure their metastatic cancer. Most participants believed treatment could provide symptom relief (76%) and extend life expectancy (95%). Among participants reporting that cancer cure was at least a little likely vs not at all, more men identified as non-white (24% vs 5%; P = .01), self-reported good health (90% vs 58%; P < .01), and had greater optimism (78% vs 47%; P < .01). Among participants reporting that symptom relief was at least a little likely vs not at all, more men were less than 70 years old (62% vs 0%; P = .01). Conclusion: A large proportion of patients with metastatic prostate cancer reported beliefs inconsistent with understanding that treatment was not curative. Race, better self-reported health, and greater optimism were related to unrealistic expectations.Efforts to ensure alignment of patient and clinician expectations may facilitate more effective shared decision-making for treating metastatic disease. K E Y W O R D S metastatic disease, prognostic understanding, prostate cancer, systemic treatments, treatment expectations How to cite this article: Oswald LB, Kasimer R, Rappazzo K, Fought AJ, Penson DF, Morgans AK. Patient expectations of benefit from systemic treatments for metastatic prostate cancer. Cancer Med. 2020;9:980-987. https ://doi.