title: Aneuploidy in Cancer and Aging.
abstract: Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs cellular fitness and prevents neoplastic transformation. Here, we suggest a new perspective to reconcile this apparent paradox and share an unexpected link between aneuploidy and aging that was discovered through attempts to investigate the CIN-cancer relationship. Additionally, we provide a comprehensive overview of the function and regulation of the anaphase-promoting complex, an E3 ubiquitin ligase that mediates high-fidelity chromosome segregation, and describe the mechanisms that lead to whole-chromosome gain or loss. With this review, we aim to expand our understanding of the role of CIN in cancer and aging with the long-term objective of harnessing this information for the advancement of patient care.
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Naylor
authors.affiliation: Department of Biochemistry and Molecular Biology.|Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 55905; email: vandeursen.jan@mayo.edu.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
mesh_terms: D000375:Aging / Q000235:genetics*; D064173:Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism; D000782:Aneuploidy; D002842:Chromatids; D043171:Chromosomal Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
chemical_list: D064173:Anaphase-Promoting Complex-Cyclosome
keywords: anaphase-promoting complex/cyclosome; chromosomal instability